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Ma A, Shi W, Chen L, Huang Z, Zhang Y, Tang Z, Jiang W, Xu M, Zhou J, Zhang W, Tang S. GRASLND regulates melanoma cell progression by targeting the miR-218-5p/STAM2 axis. J Transl Med 2024; 22:684. [PMID: 39060946 PMCID: PMC11282654 DOI: 10.1186/s12967-024-05397-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Accepted: 06/12/2024] [Indexed: 07/28/2024] Open
Abstract
BACKGROUND Increasing evidence suggests that long noncoding RNAs (lncRNAs) play important regulatory roles in biological processes and are dysregulated in numerous tumors. The lncRNA GRASLND functions as an oncogene in many cancers, but its role in skin cutaneous melanoma (SKCM) requires further investigation. METHODS SiRNA transfection, wound - healing and transwell assays were performed to evaluate the effect of GRASLND on cellular function. RESULTS The present study demonstrated that GRASLND expression is increased in SKCM tissues and cell lines. The high expression of GRASLND was correlated with poor prognosis and immunotherapy outcomes. Knockdown of GRASLND significantly inhibited cell migration and invasion. In addition, we found that miR-218-5p directly binds to its binding site on GRASLND, and GRASLND and miR-218-5p demonstrate mutual inhibition. Furthermore, the miR-218-5p inhibitor partially eliminated the knockdown of GRASLND and inhibited its expression. We also demonstrated that GRASLND acts as a miR-218-5p sponge that positively regulates STAM2 expression in SKCM cells. CONCLUSION In summary, these data suggest that GRASLND functions by regulating miR-218-5p/STAM2 expression, suggesting an important role for the lncRNA‒miRNA-mRNA functional network and a new potential therapeutic target for SKCM.
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Affiliation(s)
- Aiwei Ma
- Department of Plastic Surgery and Burns Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, 515051, China
- Plastic Surgery Institute of Shantou University Medical College, Shantou, Guangdong, 515051, China
- Shantou Plastic Surgery Clinical Research Center, Shantou, Guangdong, 515051, China
| | - Wenqi Shi
- Department of Plastic Surgery and Burns Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, 515051, China
- Plastic Surgery Institute of Shantou University Medical College, Shantou, Guangdong, 515051, China
- Shantou Plastic Surgery Clinical Research Center, Shantou, Guangdong, 515051, China
| | - Liyun Chen
- Plastic Surgery Institute of Shantou University Medical College, Shantou, Guangdong, 515051, China
- Shantou Plastic Surgery Clinical Research Center, Shantou, Guangdong, 515051, China
- Research Center of Translational Medicine, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, 515051, China
| | - Zijian Huang
- Department of Plastic Surgery and Burns Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, 515051, China
- Plastic Surgery Institute of Shantou University Medical College, Shantou, Guangdong, 515051, China
- Shantou Plastic Surgery Clinical Research Center, Shantou, Guangdong, 515051, China
| | - Yiwen Zhang
- Department of Plastic Surgery and Burns Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, 515051, China
- Plastic Surgery Institute of Shantou University Medical College, Shantou, Guangdong, 515051, China
- Shantou Plastic Surgery Clinical Research Center, Shantou, Guangdong, 515051, China
| | - Zixuan Tang
- Department of Plastic Surgery and Burns Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, 515051, China
- Plastic Surgery Institute of Shantou University Medical College, Shantou, Guangdong, 515051, China
- Shantou Plastic Surgery Clinical Research Center, Shantou, Guangdong, 515051, China
| | - Wenshi Jiang
- Department of Plastic Surgery and Burns Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, 515051, China
- Plastic Surgery Institute of Shantou University Medical College, Shantou, Guangdong, 515051, China
- Shantou Plastic Surgery Clinical Research Center, Shantou, Guangdong, 515051, China
| | - Mengjing Xu
- Department of Plastic Surgery and Burns Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, 515051, China
- Plastic Surgery Institute of Shantou University Medical College, Shantou, Guangdong, 515051, China
- Shantou Plastic Surgery Clinical Research Center, Shantou, Guangdong, 515051, China
| | - Jianda Zhou
- Department of Plastic and Reconstructive Surgery, Central South University Third Xiangya Hospital, Changsha, China
| | - Wancong Zhang
- Department of Plastic Surgery and Burns Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, 515051, China.
- Plastic Surgery Institute of Shantou University Medical College, Shantou, Guangdong, 515051, China.
- Shantou Plastic Surgery Clinical Research Center, Shantou, Guangdong, 515051, China.
| | - Shijie Tang
- Department of Plastic Surgery and Burns Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, 515051, China.
- Plastic Surgery Institute of Shantou University Medical College, Shantou, Guangdong, 515051, China.
- Shantou Plastic Surgery Clinical Research Center, Shantou, Guangdong, 515051, China.
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Rodríguez-Zorrilla S, Lorenzo-Pouso AI, Fais S, Logozzi MA, Mizzoni D, Di Raimo R, Giuliani A, García-García A, Pérez-Jardón A, Ortega KL, Martínez-González Á, Pérez-Sayáns M. Increased Plasmatic Levels of Exosomes Are Significantly Related to Relapse Rate in Patients with Oral Squamous Cell Carcinoma: A Cohort Study. Cancers (Basel) 2023; 15:5693. [PMID: 38067397 PMCID: PMC10705147 DOI: 10.3390/cancers15235693] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Revised: 11/21/2023] [Accepted: 11/29/2023] [Indexed: 04/12/2024] Open
Abstract
BACKGROUND Oral squamous cell carcinoma (OSCC) is characterized by an immunosuppressive tumor microenvironment. Their plasma-derived exosomes deliver immunomodulatory molecules and cargo that correlate significantly with clinical parameters. This study aims to assess the exosomal profile as a potential tool for early detection of relapse and long-term outcomes in OSCC patients undergoing conventional therapy. METHODS 27 OSCC patients with a median 38-month follow-up were included in this study. The relationship between NTA-derived parameters and clinical pathological parameters was examined, and receiver operating characteristic (ROC) curves were utilized to evaluate the diagnostic efficacy of these values in detecting cancer relapse. RESULTS Plasmatic levels of exosomes prior to surgery showed a drastic reduction after surgical intervention (8.08E vs. 1.41 × 109 particles/mL, p = 0.006). Postsurgical concentrations of exosomes were higher in patients who experienced relapse compared to those who remained disease-free (2.97 × 109 vs. 1.11 × 109 particles/mL, p = 0.046). Additionally, patients who relapsed exhibited larger exosome sizes after surgery (141.47 vs. 132.31 nm, p = 0.03). Patients with lower concentrations of exosomes prior to surgery demonstrated better disease-free survival compared to those with higher levels (p = 0.012). ROC analysis revealed an area under the curve of 0.82 for presurgical exosome concentration in identifying relapse. CONCLUSIONS Presurgical exosomal plasmatic levels serve as independent predictors of early recurrence and survival in OSCC. All in all, our findings indicate that the detection of peripheral exosomes represents a novel tool for the clinical management of OSCC, with potential implications for prognosis assessment.
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Affiliation(s)
- Samuel Rodríguez-Zorrilla
- Oral Medicine, Oral Surgery and Implantology Unit (MedOralRes), Faculty of Medicine and Dentistry, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain; (S.R.-Z.); (A.G.-G.); (A.P.-J.); (K.L.O.); (M.P.-S.)
| | - Alejandro I. Lorenzo-Pouso
- Oral Medicine, Oral Surgery and Implantology Unit (MedOralRes), Faculty of Medicine and Dentistry, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain; (S.R.-Z.); (A.G.-G.); (A.P.-J.); (K.L.O.); (M.P.-S.)
- ORALRES Group, Health Research Institute of Santiago de Compostela (FIDIS), 15782 Santiago de Compostela, Spain
| | - Stefano Fais
- Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy; (S.F.); (M.A.L.)
| | - Maria A. Logozzi
- Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy; (S.F.); (M.A.L.)
| | - Davide Mizzoni
- ExoLab Italia, Tecnopolo d’Abruzzo, 67100 L’Aquila, Italy; (D.M.); (R.D.R.)
| | - Rossella Di Raimo
- ExoLab Italia, Tecnopolo d’Abruzzo, 67100 L’Aquila, Italy; (D.M.); (R.D.R.)
| | - Alessandro Giuliani
- Department of Environment and Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy;
| | - Abel García-García
- Oral Medicine, Oral Surgery and Implantology Unit (MedOralRes), Faculty of Medicine and Dentistry, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain; (S.R.-Z.); (A.G.-G.); (A.P.-J.); (K.L.O.); (M.P.-S.)
- ORALRES Group, Health Research Institute of Santiago de Compostela (FIDIS), 15782 Santiago de Compostela, Spain
| | - Alba Pérez-Jardón
- Oral Medicine, Oral Surgery and Implantology Unit (MedOralRes), Faculty of Medicine and Dentistry, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain; (S.R.-Z.); (A.G.-G.); (A.P.-J.); (K.L.O.); (M.P.-S.)
- ORALRES Group, Health Research Institute of Santiago de Compostela (FIDIS), 15782 Santiago de Compostela, Spain
| | - Karem L. Ortega
- Oral Medicine, Oral Surgery and Implantology Unit (MedOralRes), Faculty of Medicine and Dentistry, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain; (S.R.-Z.); (A.G.-G.); (A.P.-J.); (K.L.O.); (M.P.-S.)
- School of Dentistry, Department of Oral Pathology, University of São Paulo, Av. Lineu Prestes, 2227, Cidade Universitária São Paulo, Sao Paulo 05508-000, Brazil
| | - Ángel Martínez-González
- Endocrinology and Nutrition Service, Complejo Hospitalario Universitario de Pontevedra, Mourente S/N, 36472 Pontevedra, Spain;
| | - Mario Pérez-Sayáns
- Oral Medicine, Oral Surgery and Implantology Unit (MedOralRes), Faculty of Medicine and Dentistry, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain; (S.R.-Z.); (A.G.-G.); (A.P.-J.); (K.L.O.); (M.P.-S.)
- ORALRES Group, Health Research Institute of Santiago de Compostela (FIDIS), 15782 Santiago de Compostela, Spain
- Institute of Materials (IMATUS), Avenida do Mestre Mateo, 25, 15782 Santiago de Compostela, Spain
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Dey S, Biswas B, Manoj Appadan A, Shah J, Pal JK, Basu S, Sur S. Non-Coding RNAs in Oral Cancer: Emerging Roles and Clinical Applications. Cancers (Basel) 2023; 15:3752. [PMID: 37568568 PMCID: PMC10417002 DOI: 10.3390/cancers15153752] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 06/29/2023] [Accepted: 07/12/2023] [Indexed: 08/13/2023] Open
Abstract
Oral cancer (OC) is among the most prevalent cancers in the world. Certain geographical areas are disproportionately affected by OC cases due to the regional differences in dietary habits, tobacco and alcohol consumption. However, conventional therapeutic methods do not yield satisfying treatment outcomes. Thus, there is an urgent need to understand the disease process and to develop diagnostic and therapeutic strategies for OC. In this review, we discuss the role of various types of ncRNAs in OC, and their promising clinical implications as prognostic or diagnostic markers and therapeutic targets. MicroRNA (miRNA), long ncRNA (lncRNA), circular RNA (circRNA), PIWI-interacting RNA (piRNA), and small nucleolar RNA (snoRNA) are the major ncRNA types whose involvement in OC are emerging. Dysregulated expression of ncRNAs, particularly miRNAs, lncRNAs, and circRNAs, are linked with the initiation, progression, as well as therapy resistance of OC via modulation in a series of cellular pathways through epigenetic, transcriptional, post-transcriptional, and translational modifications. Differential expressions of miRNAs and lncRNAs in blood, saliva or extracellular vesicles have indicated potential diagnostic and prognostic importance. In this review, we have summarized all the promising aspects of ncRNAs in the management of OC.
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Affiliation(s)
| | | | | | | | | | - Soumya Basu
- Cancer and Translational Research Centre, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth (DPU), Pimpri 411033, India; (S.D.)
| | - Subhayan Sur
- Cancer and Translational Research Centre, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth (DPU), Pimpri 411033, India; (S.D.)
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Ou C, He X, Liu Y, Zhang X. lncRNA cytoskeleton regulator RNA (CYTOR): Diverse functions in metabolism, inflammation and tumorigenesis, and potential applications in precision oncology. Genes Dis 2023; 10:415-429. [PMID: 37223495 PMCID: PMC10201560 DOI: 10.1016/j.gendis.2021.08.012] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Accepted: 08/20/2021] [Indexed: 12/19/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) are a novel class of non-coding RNA (ncRNA), that have been studied extensively in the field of tumor research in recent years. In the case of tumor-associated lncRNAs, lncRNA cytoskeleton regulator RNA (CYTOR) displays extensive functions in tumorigenesis, including invasion, metastasis, malignant proliferation, glycolysis, and inflammatory response. Moreover, the dysregulation of CYTOR is closely related to clinicopathological characteristics, such as tumor stage, lymph node metastasis and infiltration, and poor prognosis of tumor patients. In this review, we provide a novel strategy to summarize the biological functions and clinical value of CYTOR in tumors through an overview of the literature combined with gene set enrichment analysis. A deeper understanding of the role of CYTOR in tumorigenesis may provide new diagnostic, prognostic and therapeutic markers for human tumors.
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Affiliation(s)
- Chunlin Ou
- Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Xiaoyun He
- Departments of Ultrasound Imaging, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Yong Liu
- Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- Otolaryngology Major Disease Research, Key Laboratory of Hunan Province, Changsha, Hunan 410008, China
- Clinical Research Center for Pharyngolaryngeal Diseases and Voice Disorders in Hunan Province, Changsha, Hunan 410008, China
- National Clinical Research Center for Geriatric Disorders (Xiangya Hospital), Changsha, Hunan 410008, China
| | - Xin Zhang
- Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- Otolaryngology Major Disease Research, Key Laboratory of Hunan Province, Changsha, Hunan 410008, China
- Clinical Research Center for Pharyngolaryngeal Diseases and Voice Disorders in Hunan Province, Changsha, Hunan 410008, China
- National Clinical Research Center for Geriatric Disorders (Xiangya Hospital), Changsha, Hunan 410008, China
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Wu Y, Xu Y, He S, Li Y, Feng N, Fan J, Gong Y, Li X, Zhou L. Cytoskeleton regulator RNA expression on cancer-associated fibroblasts is associated with prognosis and immunotherapy response in bladder cancer. Heliyon 2023; 9:e13707. [PMID: 36873531 PMCID: PMC9976329 DOI: 10.1016/j.heliyon.2023.e13707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 01/01/2023] [Accepted: 02/08/2023] [Indexed: 02/16/2023] Open
Abstract
Background Dysregulation of long noncoding RNAs (lncRNAs) has been reported to be associated with multiple tumors where they act as tumor suppressors or accelerators. The lncRNA CYTOR was identified as an oncogene involved in many cancers, such as gastric cancer, colorectal cancer, hepatocellular carcinoma, and renal cell carcinoma. However, the role of CYTOR in bladder cancer (BCa) has rarely been reported. Methods Using cancer datasets from The Cancer Genome Atlas (TCGA) program, we analyzed the association between CYTOR expression and prognostic value, oncogenic pathways, antitumor immunity and immunotherapy response in BCa. The influence of CYTOR on the immune infiltration pattern in the urothelial carcinoma microenvironment was further verified in our dataset. Single-cell analysis revealed the role of CYTOR in the tumor microenvironment (TME) of BCa. Finally, we evaluated the expression of CYTOR in BCa in the Peking University First Hospital (PKU-BCa) dataset and its correlation with the malignant phenotype of BCa in vitro and in vivo. Results The results indicated that CYTOR was highly expressed in multiple cancer samples, including BCa, and increased CYTOR expression contributed to poor overall survival (OS). Additionally, elevated CYTOR expression was significantly correlated with clinicopathological features of BCa, such as female sex, advanced TNM stage, high histological grade and non-papillary subtype. Functional characterization revealed that CYTOR may be involved in immune-related pathways and the epithelial mesenchymal transformation (EMT) process. Moreover, CYTOR had a significant association with infiltrating immune cells, including M2 macrophages and regulatory T cells (Tregs). CYTOR facilitates the crosstalk between cancer-associated fibroblasts (CAFs) and macrophages, and mediates M2 polarization of macrophages. Correlation analysis revealed a positive correlation between CYTOR expression and programmed cell death-1 (PD-1)/programmed death ligand 1 (PD-L1)/expression and other targets for specific immunotherapy in BCa, which are recognized to predict the efficacy of immunotherapy. Conclusions These results suggest that CYTOR serves as a potential biomarker for predicting survival outcome, TME cell infiltration characteristics and immunotherapy response in BCa.
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Key Words
- BCa, Bladder cancer
- Bladder cancer
- CAFs, Cancer-associated fibroblasts
- CIBERSOFT, Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts
- CYTOR
- CYTOR, Cytoskeleton regulator RNA
- EMT, Epithelial mesenchymal transformation
- Immune infiltration
- Immunotherapy
- LncRNAs, Long non-coding RNAs
- MIBC, Muscle-invasive bladder cancer
- OS, Overall survival
- PCA, Principal component analysis
- PD-1, Programmed cell death-1
- PD-L1, Programmed death ligand 1
- RT-qPCR, Reverse transcription-quantitative polymerase chain reaction
- Survival
- TCGA, The Cancer Genome Atlas
- TME, Tumor microenvironment
- UMI, Unique molecular identifier
- UTUC, Upper-tract urothelial carcinoma
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Affiliation(s)
- Yucai Wu
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China.,Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, Peking University, Beijing, China
| | - Yangyang Xu
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China.,Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, Peking University, Beijing, China
| | - Shiming He
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China.,Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, Peking University, Beijing, China
| | - Yifan Li
- Department of Urology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Jiangsu, China
| | | | - Jian Fan
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China.,Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, Peking University, Beijing, China
| | - Yanqing Gong
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China.,Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, Peking University, Beijing, China
| | - Xuesong Li
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China.,Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, Peking University, Beijing, China
| | - Liqun Zhou
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China.,Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, Peking University, Beijing, China
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Zhao R, Wang S, Tan L, Li H, Liu J, Zhang S. IGFL2-AS1 facilitates tongue squamous cell carcinoma progression via Wnt/β-catenin signaling pathway. Oral Dis 2023; 29:469-482. [PMID: 34085359 DOI: 10.1111/odi.13935] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 05/06/2021] [Accepted: 05/26/2021] [Indexed: 02/05/2023]
Abstract
OBJECTIVES Tongue squamous cell carcinoma (TSCC) is the most common malignancy in oral cancer. Long noncoding RNAs (lncRNAs) are important regulators in cancer biology. In our present study, we investigated a novel lncRNA IGF-like family member 2 antisense RNA 1 (IGFL2-AS1) in TSCC. METHODS RT-qPCR analyzed IGFL2-AS1 expression in TSCC cells. Functional assays assessed the impact of IGFL2-AS1 on TSCC cell proliferation, migration, and invasion. Western blot analyzed the protein levels of EMT-related markers. Mechanism assays analyzed the regulatory mechanism of IGFL2-AS1 in TSCC cells. In-vivo experiments were conducted to prove the role of IGFL2-AS1 in TSCC progression. RESULTS IGFL2-AS1 was significantly up-regulated in TSCC cells and tissues, and IGFL2-AS1 knockdown inhibited cell proliferation, migration, invasion and EMT in TSCC. Moreover, IGFL2-AS1 functioned as a competing endogenous RNA (ceRNA) to sponge miR-1224-5p and thereby modulated SATB homeobox 1 (SATB1) expression. Additionally, SATB1 activated the Wnt/β-catenin signaling pathway in TSCC cells and IGFL2-AS1 regulated the Wnt/β-catenin signaling pathway and TSCC progression via elevating SATB1 expression. CONCLUSIONS The data revealed that IGFL2-AS1 played a cancer promoting role in TSCC and may aid in exploring a brand new biomarker that might contribute to TSCC treatment.
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Affiliation(s)
- Ruimin Zhao
- Department of Otorhinolaryngology Head and Neck Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Shiyang Wang
- Department of Otorhinolaryngology Head and Neck Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Lu Tan
- Department of Pediatrics, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Huajing Li
- Department of Otorhinolaryngology Head and Neck Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Junsong Liu
- Department of Otorhinolaryngology Head and Neck Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Shaoqiang Zhang
- Department of Otorhinolaryngology Head and Neck Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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Yu J, Chen X, Li J, Wang F. CERS6 antisense RNA 1 promotes colon cancer via upregulating mitochondrial calcium uniporter. Eur J Clin Invest 2023; 53:e13951. [PMID: 36628448 DOI: 10.1111/eci.13951] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 10/27/2022] [Accepted: 12/26/2022] [Indexed: 01/12/2023]
Abstract
BACKGROUND Colon cancer (CC) belongs to a common cancer of digestive system. Long non-coding RNAs (lncRNAs) are dysregulated in numerous cancers and affect their development. The function of lncRNA CERS6 antisense RNA 1 (CERS6-AS1) in CC remains unclear. MATERIALS AND METHODS CERS6-AS1 expression in colon adenocarcinoma tissues and CC cell lines was assessed by The Cancer Genome Atlas database and quantitative real-time polymerase chain reaction analysis. The function of CERS6-AS1 in CC was analysed by 5-ethynyl-2'-deoxyuridine, colony formation, flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labelling, wound healing, Transwell and immunofluorescence assays. Mechanistic analyses including RNA pull down, RNA-binding protein immunoprecipitation and luciferase reporter assay revealed the interaction between RNAs. RESULTS CERS6-AS1 expression was aberrantly upregulated in colon adenocarcinoma tissues and CC cell lines. CERS6-AS1 knockdown inhibited CC cell malignant phenotypes and in vivo tumour growth. CERS6-AS1 served as the competing endogenous RNA of microRNA-16-5p in CC, and microRNA-16-5p inhibition partly rescued the effects of CERS6-AS1 depletion on CC development. Mitochondrial calcium uniporter was targeted by microRNA-16-5p. Mitochondrial calcium uniporter upregulation completely remedied the influence of CERS6-AS1 silencing in CC progression. Moreover, CERS6-AS1 enhanced the stability of mitochondrial calcium uniporter messenger RNA via recruiting RNA-binding protein embryonic lethal abnormal vision like 1. CONCLUSION CERS6-AS1 promotes the development of CC via upregulating mitochondrial calcium uniporter expression.
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Affiliation(s)
- Juan Yu
- Endoscopic Diagnosis and Treatment Center, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Xiaoguang Chen
- Endoscopic Diagnosis and Treatment Center, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Jing Li
- Endoscopic Diagnosis and Treatment Center, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Furang Wang
- Endoscopic Diagnosis and Treatment Center, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
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Long non-coding RNAs involved in retinoblastoma. J Cancer Res Clin Oncol 2023; 149:401-421. [PMID: 36305946 DOI: 10.1007/s00432-022-04398-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 10/05/2022] [Indexed: 02/03/2023]
Abstract
INTRODUCTION Retinoblastoma (RB) is the most common childhood tumor that can occur in the retina and develop in a sporadic or heritable form. Although various traditional treatment options have been used for patients with RB, identifying novel strategies for childhood cancers is necessary. MATERIAL AND METHODS Recently, molecular-based targeted therapies have opened a greater therapeutic window for RB. Long non-coding RNAs (lncRNAs) presented a potential role as a biomarker for the detection of RB in various stages. CONCLUSION LncRNAs by targeting several miRNA/transcription factors play critical roles in the stimulation or suppression of RB. In this review, we summarized recent progress on the functions of tumor suppressors or oncogenes lncRNAs in RB.
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A review on the role of LINC00152 in different disorders. Pathol Res Pract 2023; 241:154274. [PMID: 36563561 DOI: 10.1016/j.prp.2022.154274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 12/06/2022] [Accepted: 12/08/2022] [Indexed: 12/15/2022]
Abstract
LINC00152 is an important lncRNA in human disorders. It is mainly regarded as a tumor-promoting lncRNA. Mechanistically, LINC00152 serves as a molecular sponge for miR-143a-3p, miR-125a-5p, miR-139, miR-215, miR-193a/b-3p, miR-16-5p, miR-206, miR-195, miR-138, miR-185-5p, miR-103, miR-612, miR-150, miR-107, miR-205-5p and miR-153-3p. In addition, it can regulate activity of mTOR, EGFR/PI3K/AKT, ERK/MAPK, Wnt/β-Catenin, EGFR, NF-κB, HIF-1 and PTEN. In this review, we provide a concise but comprehensive explanation about the role of LINC00152 in tumor development and progression as well as its role in the pathology of non-malignant conditions with the aim of facilitating the clinical implementation of this lncRNA as a diagnostic or prognostic tumor marker and therapeutic target.
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Sekar AA, Veeraraghavan VP, Raj AT, Patil S. Unravelling the long non-coding RNA, CYTOR can serve as a potential therapeutic target in oral cancer. Oral Oncol 2022; 135:106195. [DOI: 10.1016/j.oraloncology.2022.106195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Accepted: 10/06/2022] [Indexed: 11/05/2022]
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Li S, Yao W, Liu R, Gao L, Lu Y, Zhang H, Liang X. Long non-coding RNA LINC00152 in cancer: Roles, mechanisms, and chemotherapy and radiotherapy resistance. Front Oncol 2022; 12:960193. [PMID: 36033524 PMCID: PMC9399773 DOI: 10.3389/fonc.2022.960193] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 07/20/2022] [Indexed: 11/13/2022] Open
Abstract
Long non-coding RNA LINC00152 (cytoskeleton regulator, or LINC00152) is an 828-bp lncRNA located on chromosome 2p11.2. LINC00152 was originally discovered during research on hepatocarcinogenesis and has since been regarded as a crucial oncogene that regulates gene expression in many cancer types. LINC00152 is aberrantly expressed in various cancers, including gastric, breast, ovarian, colorectal, hepatocellular, and lung cancer, and glioma. Several studies have indicated that LINC00152 is correlated with cell proliferation, apoptosis, migration, invasion, cell cycle, epithelial-mesenchymal transition (EMT), chemotherapy and radiotherapy resistance, and tumor growth and metastasis. High LINC00152 expression in most tumors is significantly associated with poor patient prognosis. Mechanistic analysis has demonstrated that LINC00152 can serve as a competing endogenous RNA (ceRNA) by sponging miRNA, regulating the abundance of the protein encoded by a particular gene, or modulating gene expression at the epigenetic level. LINC00152 can serve as a diagnostic or prognostic biomarker, as well as a therapeutic target for most cancer types. In the present review, we discuss the roles and mechanisms of LINC00152 in human cancer, focusing on its functions in chemotherapy and radiotherapy resistance.
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Affiliation(s)
- Shuang Li
- Cancer Center, Department of Affiliated People’ Radiation Oncology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
- Graduate Department, Jinzhou Medical University, Jinzhou, China
| | - Weiping Yao
- Cancer Center, Department of Affiliated People’ Radiation Oncology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
- Graduate Department, Bengbu Medical College, Bengbu, China
| | - Ruiqi Liu
- Cancer Center, Department of Affiliated People’ Radiation Oncology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
- Graduate Department, Bengbu Medical College, Bengbu, China
| | - Liang Gao
- Cancer Center, Department of Medical Oncology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
| | - Yanwei Lu
- Cancer Center, Department of Affiliated People’ Radiation Oncology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
| | - Haibo Zhang
- Cancer Center, Department of Affiliated People’ Radiation Oncology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
- *Correspondence: Xiaodong Liang, ; Haibo Zhang,
| | - Xiaodong Liang
- Cancer Center, Department of Affiliated People’ Radiation Oncology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
- Graduate Department, Jinzhou Medical University, Jinzhou, China
- *Correspondence: Xiaodong Liang, ; Haibo Zhang,
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Fan C, Xiong F, Tang Y, Li P, Zhu K, Mo Y, Wang Y, Zhang S, Gong Z, Liao Q, Li G, Zeng Z, Guo C, Xiong W, Huang H. Construction of a lncRNA–mRNA Co-Expression Network for Nasopharyngeal Carcinoma. Front Oncol 2022; 12:809760. [PMID: 35875165 PMCID: PMC9302896 DOI: 10.3389/fonc.2022.809760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 06/06/2022] [Indexed: 11/24/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) widely regulate gene expression and play important roles in the pathogenesis of human diseases, including malignant tumors. However, the functions of most lncRNAs remain to be elucidated. In order to study and screen novel lncRNAs with important functions in the carcinogenesis of nasopharyngeal carcinoma (NPC), we constructed a lncRNA expression profile of 10 NPC tissues and 6 controls through a gene microarray. We identified 1,276 lncRNAs, of which most are unknown, with different expression levels in the healthy and NPC tissues. In order to shed light on the functions of these unknown lncRNAs, we first constructed a co-expression network of lncRNAs and mRNAs using bioinformatics and systematic biological approach. Moreover, mRNAs were clustered and enriched by their biological functions, and those lncRNAs have similar expression trends with mRNAs were defined as functional molecules with potential biological significance. The module may help identify key lncRNAs in the carcinogenesis of NPC and provide clues for in-depth study of their functions and associated signaling pathways. We suggest the newly identified lncRNAs may have clinic value as biomarkers and therapeutic targets for NPC diagnosis and treatment.
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Affiliation(s)
- Chunmei Fan
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
- Department of Histology and Embryology, Xiangya School of Medicine, Central South University, Changsha, China
- Department of Stomatology, Xiangya Hospital, Central South University, Changsha, China
| | - Fang Xiong
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
- Department of Histology and Embryology, Xiangya School of Medicine, Central South University, Changsha, China
- Department of Stomatology, Xiangya Hospital, Central South University, Changsha, China
| | - Yanyan Tang
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Panchun Li
- Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Kunjie Zhu
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Yongzhen Mo
- Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Yumin Wang
- Department of Stomatology, Xiangya Hospital, Central South University, Changsha, China
| | - Shanshan Zhang
- Department of Stomatology, Xiangya Hospital, Central South University, Changsha, China
| | - Zhaojiang Gong
- Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Qianjin Liao
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Guiyuan Li
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
- Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Zhaoyang Zeng
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
- Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Can Guo
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
- Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Wei Xiong
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
- Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
- *Correspondence: Wei Xiong, ; He Huang,
| | - He Huang
- Department of Histology and Embryology, Xiangya School of Medicine, Central South University, Changsha, China
- *Correspondence: Wei Xiong, ; He Huang,
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Bukhari I, Khan MR, Hussain MA, Thorne RF, Yu Y, Zhang B, Zheng P, Mi Y. PINTology: A short history of the lncRNA LINC-PINT in different diseases. WILEY INTERDISCIPLINARY REVIEWS. RNA 2022; 13:e1705. [PMID: 35019222 DOI: 10.1002/wrna.1705] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 11/09/2021] [Accepted: 11/17/2021] [Indexed: 12/24/2022]
Abstract
LINC-PINT is a p53-induced long intergenic noncoding transcript that plays a crucial role in many diseases, especially cancer. This long noncoding RNA (lncRNA) gene produces in total 102 (LNCipedia) alternatively spliced variants (LINC-PINT:1 to LINC-PINT:102). The functions of known variants include RNA transcripts, host transcripts for circular RNA (circRNA) generation and as sources for the translation of short peptides. In most human tumors, LINC-PINT is down-regulated where it serves as a tumor suppressor. However, the diversity of its functions in other maladies signifies its general clinical importance. Current LINC-PINT molecular functions include RNA-protein interactions, miRNA sponging and epigenetic modulation with these mechanisms operating in different cellular contexts to exert effects on biological processes ranging from DNA damage responses, cell cycle and growth arrest, senescence, cell migration and invasion, and apoptosis. Genetic polymorphisms in LINC-PINT have also been functionally associated with cancer and other pathologies including the autoimmune diseases pemphigus foliaceus and arthritis. Hence, LINC-PINT shows great potential as a clinical biomarker, especially for the diagnosis and prognosis of cancer. In this review, we explore the current knowledge highlighting the distinctive molecular functions of LINC-PINT in specific cancers and other disease states. This article is categorized under: RNA in Disease and Development > RNA in Disease.
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Affiliation(s)
- Ihtisham Bukhari
- Henan Key Laboratory of Helicobacter pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Department of Gastroenterology, Fifth Affiliated hospital of Zhengzhou University, Zhengzhou, China
| | - Muhammad Riaz Khan
- Research Center on Aging, Centre Intégré Universitaire de Santé et Services Sociaux de l'Estrie - Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada.,Department of Biochemistry and Functional Genomics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada
| | - Mohammed Amir Hussain
- Department of Biochemistry and Functional Genomics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada.,Département de Médecine, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada
| | - Rick Francis Thorne
- Translational Research Institute, Henan Provincial People's Hospital, School of Clinical Medicine, Henan University, Zhengzhou, China.,School of Environmental & Life Sciences, The University of Newcastle, Callaghan, New South Wales, Australia
| | - Yong Yu
- Henan Key Laboratory of Helicobacter pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Department of Gastroenterology, Fifth Affiliated hospital of Zhengzhou University, Zhengzhou, China
| | - Bingyong Zhang
- Department of Gastroenterology, Henan Provincial People's Hospital, School of Clinical Medicine, Henan University, Zhengzhou, China
| | - Pengyuan Zheng
- Henan Key Laboratory of Helicobacter pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Department of Gastroenterology, Fifth Affiliated hospital of Zhengzhou University, Zhengzhou, China
| | - Yang Mi
- Henan Key Laboratory of Helicobacter pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Department of Gastroenterology, Fifth Affiliated hospital of Zhengzhou University, Zhengzhou, China
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Long noncoding RNA LINC00518 contributes to proliferation and metastasis in lung adenocarcinoma via the miR-335-3p/CTHRC1 Axis. Cell Death Dis 2022; 8:98. [PMID: 35246517 PMCID: PMC8897435 DOI: 10.1038/s41420-022-00905-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Revised: 02/03/2022] [Accepted: 02/14/2022] [Indexed: 12/23/2022]
Abstract
Long intergenic nonprotein coding RNA 518 (LINC00518) is recognized to impart cancer proliferation and metastasis in lung adenocarcinoma (LUAD). However, the study about the relationship between LINC00518 and LUAD is shallow so far. In our work, LINC00518 was predicted to be a negative regulator in LUAD based on the TCGA database. It was further verified that the cell proliferation, colony formation, migration, and invasion of LUAD could be obviously inhibited by the knockdown of LINC00518. Moreover, miR-335-3p/CTHRC1 axis was intensively possible to be a critical regulator in the effect of LINC00518 on LUAD via visual ceRNA network. Importantly the progress of LUAD was relevant to the active CTHRC1 which was realized by the target of LINC00518 to miR-335-3p. Furthermore, the knockdown of LINC00518 exhibited a synergistic effect with VS6063, an inhibitor of FAK protein, in the suppression of LUAD indicating that miR-335-3p/CTHRC1 axis was potentially exploitable as a targeted intervention to integrin β3/FAK signal pathway in LUAD. All the collective results demonstrated that LINC00518 could be a promising biomarker of the prognosis of LUAD and possibly a therapeutic target via miR-335-3p/CTHRC1 axis.
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The association of long non-coding RNA in the prognosis of oral squamous cell carcinoma. Genes Genomics 2022; 44:327-342. [PMID: 35023067 DOI: 10.1007/s13258-021-01194-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 11/17/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND Oral cancer is considered one of the most prevalent cancers in India. This is mainly because India suffers from high usage of tobacco, which is one of the main causative agents of oral cancer, and lacks proper health and sexual hygiene in rural areas. DISCUSSION Non-coding RNAs are reported to be involved in the various mechanism and causality of cancer. Numerous reports have identified viable prospects connecting non-coding RNA (ncRNA) with cancer. Specific ncRNAs like long non-coding RNA or lncRNAs are recently being prioritized as potential associations in the cause of cancer. CONCLUSION This review aims at presenting a concise perspective on the basics and the recent advancements of the lncRNA research pertaining specifically to oral cancer, its recurrence, and the future possibilities of knowledge it might possess.
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Yang M, Zhang Y, Zhou Y, Zhao T, Li Z, Yue H, Piao Z. Analysis of the expression profiles of long noncoding RNAs and messenger RNAs in tongue squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol 2022; 134:230-239. [PMID: 35725960 DOI: 10.1016/j.oooo.2022.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 11/22/2021] [Accepted: 01/04/2022] [Indexed: 11/28/2022]
Abstract
OBJECTIVE Long noncoding RNAs (lncRNAs) are involved in the progression of tongue squamous cell carcinoma (TSCC). Therefore, it is necessary to comprehensively investigate the role of lncRNAs in TSCC. STUDY DESIGN In this study, RNA sequencing was performed to examine the expression profiles of lncRNAs and messenger RNAs (mRNAs) of patients with TSCC. The expression of selected lncRNAs in TSCC and paired adjacent tissues as well as in cell lines was validated via quantitative real-time polymerase chain reaction (qRT-PCR). The cell function of lncRNA iodothyronine deiodinase 2 antisense RNA 1 (DIO2-AS1) overexpression was assessed through 5-(3-carboxymethoxyphenyl)-2-(4.5-dimethyl-thiazoly)-3-(4-sulfophenyl) tetrazolium inner salt and Transwell assays. RESULTS A total of 342 lncRNAs and 6392 mRNAs were differentially expressed in TSCC tissues compared with paired adjacent tissues. qRT-PCR revealed the increased expression of AC093818.1 and reduced expression of CYP4F35P and DIO2-AS1 in TSCC. Furthermore, DIO2-AS1 overexpression inhibited Cal-27 cell proliferation, migration, and invasion. CONCLUSIONS We provide evidence that DIO2-AS1 is involved in TSCC progression. This study provides a direction for subsequent research.
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Affiliation(s)
- Mi Yang
- Department of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou 510182, Guangdong, China
| | - Yumin Zhang
- Department of Pediatric Stomatology, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou 510182, Guangdong, China
| | - Yang Zhou
- Department of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou 510182, Guangdong, China
| | - Tianyu Zhao
- Department of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou 510182, Guangdong, China
| | - Zhicong Li
- Department of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou 510182, Guangdong, China
| | - Haiqiong Yue
- Department of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou 510182, Guangdong, China
| | - Zhengguo Piao
- Department of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou 510182, Guangdong, China.
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Tang J, Fang X, Chen J, Zhang H, Tang Z. Long Non-Coding RNA (lncRNA) in Oral Squamous Cell Carcinoma: Biological Function and Clinical Application. Cancers (Basel) 2021; 13:cancers13235944. [PMID: 34885054 PMCID: PMC8656574 DOI: 10.3390/cancers13235944] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Revised: 11/22/2021] [Accepted: 11/24/2021] [Indexed: 12/11/2022] Open
Abstract
Simple Summary Increasing evidence has revealed the regulatory roles of long non-coding RNAs (lncRNAs) in the initiation and progress of oral squamous cell carcinoma (OSCC). As some novel lncRNA-targeted techniques combined with immune checkpoint therapies have emerged, they provide a new strategy for OSCC treatment. This review summarizes current knowledge regarding the involvement of lncRNAs in OSCC along with their possible use as diagnostic and prognostic biomarker and therapeutic targets. Abstract Oral squamous cell carcinoma (OSCC) is a type of malignancy with high mortality, leading to poor prognosis worldwide. However, the molecular mechanisms underlying OSCC carcinogenesis have not been fully understood. Recently, the discovery and characterization of long non-coding RNAs (lncRNAs) have revealed their regulatory importance in OSCC. Abnormal expression of lncRNAs has been broadly implicated in the initiation and progress of tumors. In this review, we summarize the functions and molecular mechanisms regarding these lncRNAs in OSCC. In addition, we highlight the crosstalk between lncRNA and tumor microenvironment (TME), and discuss the potential applications of lncRNAs as diagnostic and prognostic tools and therapeutic targets in OSCC. Notably, we also discuss lncRNA-targeted therapeutic techniques including CRISPR-Cas9 as well as immune checkpoint therapies to target lncRNA and the PD-1/PD-L1 axis. Therefore, this review presents the future perspectives of lncRNAs in OSCC therapy, but more research is needed to allow the applications of these findings to the clinic.
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Affiliation(s)
- Jianfei Tang
- Hunan Key Laboratory of Oral Health Research, Central South University, Changsha 410008, China; (J.T.); (X.F.); (J.C.)
- Hunan 3D Printing Engineering Research Center of Oral Care, Central South University, Changsha 410008, China
- Hunan Clinical Research Center of Oral Major Diseases and Oral Health, Central South University, Changsha 410008, China
- Xiangya Stomatological Hospital, Central South University, Changsha 410008, China
- Xiangya School of Stomatology, Central South University, Changsha 410008, China
| | - Xiaodan Fang
- Hunan Key Laboratory of Oral Health Research, Central South University, Changsha 410008, China; (J.T.); (X.F.); (J.C.)
- Hunan 3D Printing Engineering Research Center of Oral Care, Central South University, Changsha 410008, China
- Hunan Clinical Research Center of Oral Major Diseases and Oral Health, Central South University, Changsha 410008, China
- Xiangya Stomatological Hospital, Central South University, Changsha 410008, China
- Xiangya School of Stomatology, Central South University, Changsha 410008, China
| | - Juan Chen
- Hunan Key Laboratory of Oral Health Research, Central South University, Changsha 410008, China; (J.T.); (X.F.); (J.C.)
- Hunan 3D Printing Engineering Research Center of Oral Care, Central South University, Changsha 410008, China
- Hunan Clinical Research Center of Oral Major Diseases and Oral Health, Central South University, Changsha 410008, China
- Xiangya Stomatological Hospital, Central South University, Changsha 410008, China
- Xiangya School of Stomatology, Central South University, Changsha 410008, China
| | - Haixia Zhang
- The Oncology Department of Xiangya Second Hospital, Central South University, Changsha 410008, China
- Correspondence: (H.Z.); (Z.T.); Tel.: +86-139-7313-0429 (H.Z.); +86-139-0731-7983 (Z.T.)
| | - Zhangui Tang
- Hunan Key Laboratory of Oral Health Research, Central South University, Changsha 410008, China; (J.T.); (X.F.); (J.C.)
- Hunan 3D Printing Engineering Research Center of Oral Care, Central South University, Changsha 410008, China
- Hunan Clinical Research Center of Oral Major Diseases and Oral Health, Central South University, Changsha 410008, China
- Xiangya Stomatological Hospital, Central South University, Changsha 410008, China
- Xiangya School of Stomatology, Central South University, Changsha 410008, China
- Correspondence: (H.Z.); (Z.T.); Tel.: +86-139-7313-0429 (H.Z.); +86-139-0731-7983 (Z.T.)
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Xu BH, Jiang JH, Luo T, Jiang ZJ, Liu XY, Li LQ. Signature of prognostic epithelial-mesenchymal transition related long noncoding RNAs (ERLs) in hepatocellular carcinoma. Medicine (Baltimore) 2021; 100:e26762. [PMID: 34397721 PMCID: PMC8322489 DOI: 10.1097/md.0000000000026762] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 07/04/2021] [Indexed: 01/04/2023] Open
Abstract
Reliable biomarkers are of great significance for the treatment and diagnosis of hepatocellular carcinoma (HCC). This study identified potential prognostic epithelial-mesenchymal transition related lncRNAs (ERLs) by the cancer genome atlas (TCGA) database and bioinformatics.The differential expression of long noncoding RNA (lncRNA) was obtained by analyzing the lncRNA data of 370 HCC samples in TCGA. Then, Pearson correlation analysis was carried out with EMT related genes (ERGs) from molecular signatures database. Combined with the univariate Cox expression analysis of the total survival rate of hepatocellular carcinoma (HCC) patients, the prognostic ERLs were obtained. Then use "step" function to select the optimal combination of constructing multivariate Cox expression model. The expression levels of ERLs in HCC samples were verified by real-time quantitative polymerase chain reaction.Finally, we identified 5 prognostic ERLs (AC023157.3, AC099850.3, AL031985.3, AL365203.2, CYTOR). The model showed that these prognostic markers were reliable independent predictors of risk factors (P value <.0001, hazard ratio [HR] = 2.400, 95% confidence interval [CI] = 1.667-3.454 for OS). In the time-dependent receiver operating characteristic analysis, this prognostic marker is a good predictor of HCC survival (area under the curve of 1 year, 2 years, 3 years, and 5 years are 0.754, 0.720, 0.704, and 0.662 respectively). We analyzed the correlation of clinical characteristics of these prognostic markers, and the results show that this prognostic marker is an independent factor that can predict the prognosis of HCC more accurately. In addition, by matching with the Molecular Signatures Database, we obtained 18 ERLs, and then constructed the HCC prognosis model and clinical feature correlation analysis using 5 prognostic ERLs. The results show that these prognostic markers have reliable independent predictive value. Bioinformatics analysis showed that these prognostic markers were involved in the regulation of EMT and related functions of tumor occurrence and migration.Five prognostic types of ERLs identified in this study can be used as potential biomarkers to predict the prognosis of HCC.
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Affiliation(s)
- Bang-Hao Xu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Jing-Hang Jiang
- Department of Hepatobiliary Surgery, Jing Men NO.2 People's Hospital, Jingmen, Hubei, China
| | - Tao Luo
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Nanning, Guangxi, China
| | - Zhi-Jun Jiang
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Nanning, Guangxi, China
| | - Xin-Yu Liu
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Nanning, Guangxi, China
| | - Le-Qun Li
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Tumor Hospital, Nanning, Guangxi, China
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Long non-coding RNA AFAP1-AS1 accelerates lung cancer cells migration and invasion by interacting with SNIP1 to upregulate c-Myc. Signal Transduct Target Ther 2021; 6:240. [PMID: 34168109 PMCID: PMC8225811 DOI: 10.1038/s41392-021-00562-y] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Revised: 01/29/2021] [Accepted: 03/16/2021] [Indexed: 12/13/2022] Open
Abstract
Actin filament associated protein 1 antisense RNA 1 (named AFAP1-AS1) is a long non-coding RNA and overexpressed in many cancers. This study aimed to identify the role and mechanism of AFAP1-AS1 in lung cancer. The AFAP1-AS1 expression was firstly assessed in 187 paraffin-embedded lung cancer and 36 normal lung epithelial tissues by in situ hybridization. The migration and invasion abilities of AFAP1-AS1 were investigated in lung cancer cells. To uncover the molecular mechanism about AFAP1-AS1 function in lung cancer, we screened proteins that interact with AFAP1-AS1 by RNA pull down and the mass spectrometry analyses. AFAP1-AS1 was highly expressed in lung cancer clinical tissues and its expression was positively correlated with lung cancer patients’ poor prognosis. In vivo experiments confirmed that AFAP1-AS1 could promote lung cancer metastasis. AFAP1-AS1 promoted lung cancer cells migration and invasion through interacting with Smad nuclear interacting protein 1 (named SNIP1), which inhibited ubiquitination and degradation of c-Myc protein. Upregulation of c-Myc molecule in turn promoted the expression of ZEB1, ZEB2, and SNAIL gene, which ultimately enhanced epithelial to mesenchymal transition (EMT) and lung cancer metastasis. Understanding the molecular mechanism by which AFAP1-AS1 promotes lung cancer’s migration and invasion may provide novel therapeutic targets for lung cancer patients’ early diagnosis and therapy.
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Xiong F, Zhu K, Deng S, Huang H, Yang L, Gong Z, Shi L, He Y, Tang Y, Liao Q, Yu J, Li X, Li Y, Li G, Zeng Z, Xiong W, Zhang S, Guo C. AFAP1-AS1: a rising star among oncogenic long non-coding RNAs. SCIENCE CHINA-LIFE SCIENCES 2021; 64:1602-1611. [PMID: 33999309 DOI: 10.1007/s11427-020-1874-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Accepted: 12/13/2020] [Indexed: 12/13/2022]
Abstract
Long non-coding RNAs (lncRNAs) have become a hotspot in biomedical research. This interest reflects their extensive involvement in the regulation of the expression of other genes, and their influence on the occurrence and development of a variety of human diseases. Actin filament associated protein 1-Antisense RNA 1(AFAP1-AS1) is a recently discovered oncogenic lncRNA. It is highly expressed in a variety of solid tumors, and regulates the expression of downstream genes and signaling pathways through adsorption and competing microRNAs, or by the direct binding to other proteins. Ultimately, AFAP1-AS1 promotes proliferation, chemotherapy resistance, and resistance to apoptosis, maintains stemness, and enhances invasion and migration of tumor cells. This paper summarizes the research concerning AFAP1-AS1 in malignant tumors, including the clinical application prospects of AFAP1-AS1 as a potential molecular marker and therapeutic target of malignant tumors. We also discuss the limitations in the knowledge of AFAP1-AS1 and directions of further research. AFAP1-AS1 is expected to provide an example for studies of other lncRNA molecules.
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Affiliation(s)
- Fang Xiong
- Science and Technology on Information System Engineering Laboratory, National University of Defense Technology, Changsha, 410000, China
- Department of Periodontology, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, 410078, China
- NHC Key Laboratory of Carcinogenesis and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education of China, Cancer Research Institute, Central South University, Changsha, 410078, China
| | - Kunjie Zhu
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China
| | - Su Deng
- Science and Technology on Information System Engineering Laboratory, National University of Defense Technology, Changsha, 410000, China
| | - Hongbin Huang
- Science and Technology on Information System Engineering Laboratory, National University of Defense Technology, Changsha, 410000, China
| | - Liting Yang
- Department of Periodontology, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, 410078, China
| | - Zhaojian Gong
- Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital Central South University, Changsha, 410011, China
| | - Lei Shi
- Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital Central South University, Changsha, 410011, China
| | - Yi He
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China
| | - Yanyan Tang
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China
| | - Qianjin Liao
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China
| | - Jianjun Yu
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China
| | - Xiaoling Li
- NHC Key Laboratory of Carcinogenesis and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education of China, Cancer Research Institute, Central South University, Changsha, 410078, China
| | - Yong Li
- Department of Medicine, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA
| | - Guiyuan Li
- NHC Key Laboratory of Carcinogenesis and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education of China, Cancer Research Institute, Central South University, Changsha, 410078, China
| | - Zhaoyang Zeng
- NHC Key Laboratory of Carcinogenesis and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education of China, Cancer Research Institute, Central South University, Changsha, 410078, China
| | - Wei Xiong
- NHC Key Laboratory of Carcinogenesis and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education of China, Cancer Research Institute, Central South University, Changsha, 410078, China
| | - Shanshan Zhang
- Department of Periodontology, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, 410078, China.
| | - Can Guo
- NHC Key Laboratory of Carcinogenesis and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education of China, Cancer Research Institute, Central South University, Changsha, 410078, China.
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21
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Li J, Fan S, Liu S, Yang G, Jin Q, Xiao Z. LncRNA NOP14-AS1 Promotes Tongue Squamous Cell Carcinoma Progression by Targeting MicroRNA-665/HMGB3 Axis. Cancer Manag Res 2021; 13:2821-2834. [PMID: 33814931 PMCID: PMC8009347 DOI: 10.2147/cmar.s293322] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Accepted: 02/04/2021] [Indexed: 12/18/2022] Open
Abstract
Purpose The expression profile, clinical effects, and detailed roles of NOP14 antisense RNA 1 (NOP14-AS1) in tongue squamous cell carcinoma (TSCC) remain ambiguous and need to be further explored. Thus, this work was initiated to offer further solid evidence regarding the expression and roles of NOP14-AS1 in TSCC. Furthermore, additional efforts were exerted to reveal the molecular events by which NOP14-AS1 affects the malignant behaviours of TSCC. Methods NOP14-AS1 expression was detected in TSCC tissues and cell lines using quantitative reverse transcription-polymerase chain reaction. Cell Counting Kit-8 assay, flow cytometric analysis, Transwell migration and invasion assays, and xenograft tumor model analysis were performed to assess the malignant biological behaviors of TSCC cells after NOP14-AS1 depletion. Mechanistic studies were performed using bioinformatics analysis, luciferase reporter assay, RNA immunoprecipitation, and rescue experiments. Results NOP14-AS1 upregulation was identified in TSCC tissues and cell lines. Patients with TSCC exhibiting a high NOP14-AS1 expression faced shorter overall survival than those with a low NOP14-AS1 expression. Functionally, NOP14-AS1 depletion facilitated apoptosis and impeded cell proliferation, migration, and invasion in TSCC. In vivo, the growth of TSCC cells was hindered by NOP14-AS1 depletion. Mechanically, NOP14-AS1 functioned as a competing endogenous RNA by sponging microRNA-665 (miR-665), thereby overexpressing the target high mobility group box 3 (HMGB3) of miR-665. Lastly, rescue experiments confirmed that the introduction of HMGB3 overexpression plasmid or miR-665 inhibitor could abrogate the inhibition of aggressive phenotypes triggered by NOP14-AS1 knockdown. Conclusion NOP14-AS1 executed pro-oncogenic activities in TSCC cells by targeting the miR-665/HMGB3 axis. The NOP14-AS1/miR-665/HMGB pathway may be a valuable prognostic indicator and therapeutic target for preventing TSCC.
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Affiliation(s)
- Jiayi Li
- Department of Stomatology, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, 161000, People's Republic of China
| | - Shuxia Fan
- Department of Stomatology, Qiqihaer Eye & ENT Hospital, Qiqihar, Heilongjiang, 161000, People's Republic of China
| | - Shuang Liu
- Department of Stomatology, The First Hospital of Qiqihar (The Affiliated Qiqihar Hospital of Southern Medical University), Qiqihar, Heilongjiang, 161000, People's Republic of China
| | - Guang Yang
- Department of Stomatology, The First Hospital of Qiqihar (The Affiliated Qiqihar Hospital of Southern Medical University), Qiqihar, Heilongjiang, 161000, People's Republic of China
| | - Qingsong Jin
- Department of Stomatology, The First Hospital of Qiqihar (The Affiliated Qiqihar Hospital of Southern Medical University), Qiqihar, Heilongjiang, 161000, People's Republic of China
| | - Zhen Xiao
- Department of Stomatology, The First Hospital of Qiqihar (The Affiliated Qiqihar Hospital of Southern Medical University), Qiqihar, Heilongjiang, 161000, People's Republic of China
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Akbari Dilmaghani N, Khoshsirat S, Shanaki-Bavarsad M, Pourbagheri-Sigaroodi A, Bashash D. The contributory role of long non-coding RNAs (lncRNAs) in head and neck cancers: Possible biomarkers and therapeutic targets? Eur J Pharmacol 2021; 900:174053. [PMID: 33766619 DOI: 10.1016/j.ejphar.2021.174053] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 03/12/2021] [Accepted: 03/17/2021] [Indexed: 12/12/2022]
Abstract
Along with the developments in techniques for genome study, our understanding of its sequences has completely changed. The non-coding sequences of the human genome are no longer considered as "junk" but are rather known to be the source of high-functioning molecules. Some of the most fascinating transcripts in this regard are long non-coding RNAs (lncRNAs) ___RNA molecules that exceed 200 nucleotides and are not transcribed from protein-coding regions of the genome. These transcripts are capable of gene regulation by various mechanisms, from epigenetic changes and chromosomal arrangements to post-transcription modulation of messenger RNAs. Furthermore, lncRNAs interact with other non-coding transcripts such as microRNAs that further affects gene expression. Considering the fact that cancer is a disease of deregulated expression, recent studies have identified lncRNAs acting as either oncogene or tumor suppressor in a wide range of human malignancies. Head and neck cancer (HNC), with a high incidence rate and unfavorable survival, is no exception in this matter and many investigations have introduced lncRNAs involved in its tumor progression and drug response, as well as those acting as promising diagnostic or prognostic markers. The present study reviews the vital regulatory roles of lncRNAs and further introduces their role in progression of HNC subtypes.
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Affiliation(s)
- Nader Akbari Dilmaghani
- Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Otolaryngology, Head and Neck Surgery, Loghman Hakim Educational Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shahrokh Khoshsirat
- Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Otolaryngology, Head and Neck Surgery, Loghman Hakim Educational Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mahsa Shanaki-Bavarsad
- Institute of Neuroscience. Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain; Department of Cell Biology, Physiology and Immunology. Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain
| | - Atieh Pourbagheri-Sigaroodi
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Davood Bashash
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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23
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Liu Y, He D, Xiao M, Zhu Y, Zhou J, Cao K. Long noncoding RNA LINC00518 induces radioresistance by regulating glycolysis through an miR-33a-3p/HIF-1α negative feedback loop in melanoma. Cell Death Dis 2021; 12:245. [PMID: 33664256 PMCID: PMC7933330 DOI: 10.1038/s41419-021-03523-z] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Revised: 02/07/2021] [Accepted: 02/09/2021] [Indexed: 01/31/2023]
Abstract
The long noncoding RNA, LINC00518, is highly expressed in various types of cancers and is involved in cancer progression. Although LINC00518 promotes the metastasis of cutaneous malignant melanoma (CMM), the mechanism underlaying its effects on CMM radiosensitivity remains unclear. In this study, LINC00518 expression was significantly upregulated in CMM samples, and LINC00518 levels were associated with poor prognosis of patients with CMM. Knockdown of LINC00518 in CMM cells significantly inhibited cell invasion, migration, proliferation, and clonogenicity. LINC00518-mediated invasion, migration, proliferation, and clonogenicity were negatively regulated by the microRNA, miR-33a-3p, in vitro, which increased sensitivity to radiotherapy via inhibition of the hypoxia-inducible factor 1α (HIF-1α)/lactate dehydrogenase A glycolysis axis. Additionally, HIF-1α recognized the miR-33a-3p promoter region and recruited histone deacetylase 2, which decreased the expression of miR-33a-3p and formed an LINC00518/miR-33a-3p/HIF-1α negative feedback loop. Furthermore, signaling with initially activated glycolysis and radioresistance in CMM cells was impaired by Santacruzamate A, a histone deacetylase inhibitor, and 2-deoxy-D-glucose, a glycolytic inhibitor. Lastly, knockdown of LINC00518 expression sensitized CMM cancer cells to radiotherapy in an in vivo subcutaneously implanted tumor model. In conclusion, LINC00518 was confirmed to be an oncogene in CMM, which induces radioresistance by regulating glycolysis through an miR-33a-3p/HIF-1α negative feedback loop. Our study, may provide a potential strategy to improve the treatment outcome of radiotherapy in CMM.
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MESH Headings
- Animals
- Cell Line, Tumor
- Cell Movement
- Cell Proliferation
- Databases, Genetic
- Feedback, Physiological
- Gene Expression Regulation, Neoplastic
- Glycolysis
- Humans
- Hypoxia-Inducible Factor 1, alpha Subunit/genetics
- Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
- Male
- Melanoma/genetics
- Melanoma/metabolism
- Melanoma/pathology
- Melanoma/radiotherapy
- Mice, Inbred BALB C
- Mice, Nude
- MicroRNAs/genetics
- MicroRNAs/metabolism
- Neoplasm Invasiveness
- RNA, Long Noncoding/genetics
- RNA, Long Noncoding/metabolism
- Radiation Tolerance
- Signal Transduction
- Skin Neoplasms/genetics
- Skin Neoplasms/metabolism
- Skin Neoplasms/pathology
- Skin Neoplasms/radiotherapy
- Tumor Hypoxia
- Tumor Microenvironment
- Xenograft Model Antitumor Assays
- Mice
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Affiliation(s)
- Yan Liu
- Department of Oncology, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, PR China
- Department of Plastic Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, PR China
| | - Dong He
- Department of Respiration, the Second People's Hospital of Hunan Province of Hunan University of Chinese Medicine, Changsha, 410000, PR China
| | - Mengqing Xiao
- Department of Oncology, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, PR China
| | - Yuxing Zhu
- Department of Oncology, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, PR China
| | - Jianda Zhou
- Department of Plastic Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, PR China
| | - Ke Cao
- Department of Oncology, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, PR China.
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Gutiérrez-Díez PJ, Gomez-Pilar J, Hornero R, Martínez-Rodríguez J, López-Marcos MA, Russo J. The role of gene to gene interaction in the breast's genomic signature of pregnancy. Sci Rep 2021; 11:2643. [PMID: 33514799 PMCID: PMC7846553 DOI: 10.1038/s41598-021-81704-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Accepted: 12/18/2020] [Indexed: 12/20/2022] Open
Abstract
Full-term pregnancy at an early age confers long-term protection against breast cancer. Published data shows a specific transcriptomic profile controlling chromatin remodeling that could play a relevant role in the pregnancy-induced protection. This process of chromatin remodeling, induced by the breast differentiation caused by the first full-term pregnancy, has mainly been measured by the expression level of genes individually considered. However, genes equally expressed during the process of chromatin remodeling may behave differently in their interaction with other genes. These changes at the gene cluster level could constitute an additional dimension of chromatin remodeling and therefore of the pregnancy-induced protection. In this research, we apply Information and Graph Theories, Differential Co-expression Network Analysis, and Multiple Regression Analysis, specially designed to examine structural and informational aspects of data sets, to analyze this question. Our findings demonstrate that, independently of the changes in the gene expression at the individual level, there are significant changes in gene-gene interactions and gene cluster behaviors. These changes indicate that the parous breast, through the process of early full-term pregnancy, generates more modules in the networks, with higher density, and a genomic structure performing additional and more complex functions than those found in the nulliparous breast.
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Affiliation(s)
- Pedro J Gutiérrez-Díez
- IMUVA Mathematical Institute, University of Valladolid, Valladolid, Spain
- Faculty of Economics, University of Valladolid, Valladolid, Spain
| | - Javier Gomez-Pilar
- Biomedical Engineering Group, University of Valladolid, Paseo de Belén, 15, 47011, Valladolid, Spain.
- Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales Y Nanomedicina (CIBER-BBN), Valladolid, Spain.
| | - Roberto Hornero
- IMUVA Mathematical Institute, University of Valladolid, Valladolid, Spain
- Biomedical Engineering Group, University of Valladolid, Paseo de Belén, 15, 47011, Valladolid, Spain
- Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales Y Nanomedicina (CIBER-BBN), Valladolid, Spain
| | - Julia Martínez-Rodríguez
- IMUVA Mathematical Institute, University of Valladolid, Valladolid, Spain
- Faculty of Economics, University of Valladolid, Valladolid, Spain
| | - Miguel A López-Marcos
- IMUVA Mathematical Institute, University of Valladolid, Valladolid, Spain
- Faculty of Science, University of Valladolid, Valladolid, Spain
| | - Jose Russo
- The Irma H. Russo, MD Breast Cancer Research Laboratory, Fox Chase Cancer Center - Temple University Health System, Philadelphia, USA
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Xu Y, Jiang E, Shao Z, Shang Z. Long Noncoding RNAs in the Metastasis of Oral Squamous Cell Carcinoma. Front Oncol 2021; 10:616717. [PMID: 33520725 PMCID: PMC7845733 DOI: 10.3389/fonc.2020.616717] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Accepted: 11/26/2020] [Indexed: 12/13/2022] Open
Abstract
Oral squamous cell carcinoma (OSCC) is a common malignant tumor worldwide. Metastasis is the main cause of the death of OSCC patients. Long noncoding RNAs (lncRNAs), one of the key factors affecting OSCC metastasis, are a subtype of RNA with a length of more than 200 nucleotides that has little or no coding potential. In recent years, the important role played by lncRNAs in biological processes, such as chromatin modification, transcription regulation, RNA stability regulation, and mRNA translation, has been gradually revealed. More and more studies have shown that lncRNAs can regulate the metastasis of various tumors including OSCC at epigenetic, transcriptional, and post-transcriptional levels. In this review, we mainly discussed the role and possible mechanisms of lncRNAs in OSCC metastasis. Most lncRNAs act as oncogenes and only a few lncRNAs have been shown to inhibit OSCC metastasis. Besides, we briefly introduced the research status of cancer-associated fibroblasts-related lncRNAs in OSCC metastasis. Finally, we discussed the research prospects of lncRNAs-mediated crosstalk between OSCC cells and the tumor microenvironment in OSCC metastasis, especially the potential research value of exosomes and lymphangiogenesis. In general, lncRNAs are expected to be used for screening, treatment, and prognosis monitoring of OSCC metastasis, but more work is still required to better understand the biological function of lncRNAs.
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Affiliation(s)
- Yuming Xu
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Erhui Jiang
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Zhe Shao
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Zhengjun Shang
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China
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26
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Abstract
Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases. The pathogenesis of NSCLC involves complex gene networks that include different types of non-coding RNAs, such as long non-coding RNAs (lncRNAs). The role of lncRNAs in NSCLC is gaining an increasing interest as their function is being explored in various human cancers. Recently, a new oncogenic lncRNA, LINC00152 (cytoskeleton regulator RNA (CYTOR)), has been identified in different tumor types. In NSCLC, the high expression of LINC00152 in tumor tissue and peripheral blood samples has been shown to be associated with worse prognoses of NSCLC patients. Overexpression of LINC00152 has been confirmed to promote the proliferation, invasion, and migration of NSCLC cells in vitro, as well as increase tumor growth in vivo. This review discusses the role of LINC00152 in NSCLC.
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Affiliation(s)
- Hong Yu
- Cell Biology Laboratory, Jilin Province Institute of Cancer Prevention and Treatment, Jilin Cancer Hospital, Changchun 130012, China
| | - Shu-Bin Li
- Department of Internal Medicine, Southern Branch of Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 102600, China
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27
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Hou C, Dong Y, Du B. Long Non-Coding RNA LINC00466 Knockdown Inhibits Tongue Squamous Cell Carcinoma Malignancy by Targeting microRNA-493/HMGA2. Cancer Manag Res 2020; 12:13071-13084. [PMID: 33376400 PMCID: PMC7764812 DOI: 10.2147/cmar.s282625] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 11/23/2020] [Indexed: 01/12/2023] Open
Abstract
Purpose Long intergenic non-protein-coding RNA 00466 (LINC00466) promotes lung adenocarcinoma progression. Nonetheless, the expression and precise roles of LINC00466 in tongue squamous cell carcinoma (TSCC) remains uncertain and warrant further investigation. Hence, the present study aimed to examine the LINC00466 effects on the aggressive TSCC cell characteristics and to elucidate the potential underlying mechanisms. Methods First, LINC00466 expression in TSCC was determined by reverse transcription-quantitative PCR. Subsequently, cell proliferation, apoptosis, migration, and invasion in vitro, as well as tumor growth in vivo were assessed to examine the LINC00466 effects on TSCC cells. Results LINC00466 was upregulated in TSCC. This upregulation was notably associated with shorter overall TSCC patient survival. In vitro experiments indicated that LINC00466 depletion suppressed TSCC cell proliferation, migration and invasion, and promoted apoptosis. An in vivo experiment revealed that LINC00466 downregulation attenuated TSCC tumor growth in vivo. Mechanistic analysis revealed that LINC00466 functions as a microRNA-493 (miR-493) molecular sponge, a miRNA that targets high-mobility group AT-hook 2 (HMGA2) mRNA. LINC00466 upregulated HMGA2 in TSCC cells, and this phenomenon was regulated by the miR-493 sponge. Rescue experiments revealed a decrease in the miR-493/HMGA2 axis output, partially reversing the effects of LINC00466 downregulation on aggressive TSCC cell behavior. Conclusion These findings demonstrate that LINC00466 promotes TSCC cell oncogenicity in vitro and in vivo by upregulating the miR-493/HMGA2 axis output. These results may provide a new perspective and new insight into the molecular mechanisms of TSCC.
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Affiliation(s)
- Chao Hou
- Department of Stomatology, Zaozhuang Municipal Hospital, Zaozhuang, Shandong 277100, People's Republic of China
| | - Yanli Dong
- Department of Stomatology, Zaozhuang Municipal Hospital, Zaozhuang, Shandong 277100, People's Republic of China
| | - Bo Du
- Department of Stomatology, Zaozhuang Municipal Hospital, Zaozhuang, Shandong 277100, People's Republic of China
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28
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Galamb O, Kalmár A, Sebestyén A, Dankó T, Kriston C, Fűri I, Hollósi P, Csabai I, Wichmann B, Krenács T, Barták BK, Nagy ZB, Zsigrai S, Barna G, Tulassay Z, Igaz P, Molnár B. Promoter Hypomethylation and Increased Expression of the Long Non-coding RNA LINC00152 Support Colorectal Carcinogenesis. Pathol Oncol Res 2020; 26:2209-2223. [PMID: 32307642 PMCID: PMC7471146 DOI: 10.1007/s12253-020-00800-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Accepted: 02/27/2020] [Indexed: 12/27/2022]
Abstract
Up-regulation of the long non-coding RNA LINC00152 can contribute to cancer development, proliferation and invasion, including colorectal cancer, however, its mechanism of action in colorectal carcinogenesis and progression is only insufficiently understood. In this work we correlated LINC00152 expression with promoter DNA methylation changes in colorectal tissues along the normal-adenoma-carcinoma sequence and studied the effects of LINC00152 silencing on the cell cycle regulation and on the whole transcriptome in colon carcinoma cells using cell and molecular biology techniques. LINC00152 was significantly up-regulated in adenoma and colorectal cancer (p < 0.001) compared to normal samples, which was confirmed by real-time PCR and in situ hybridization. LINC00152 promoter hypomethylation detected in colorectal cancer (p < 0.01) was strongly correlated with increased LINC00152 expression (r=-0.90). Silencing of LINC00152 significantly suppressed cell growth, induced apoptosis and decreased cyclin D1 expression (p < 0.05). Whole transcriptome analysis of LINC00152-silenced cells revealed significant down-regulation of oncogenic and metastasis promoting genes (e.g. YES proto-oncogene 1, PORCN porcupine O-acyltransferase), and up-regulation of tumour suppressor genes (e.g. DKK1 dickkopf WNT signalling pathway inhibitor 1, PERP p53 apoptosis effector) (adjusted p < 0.05). Pathway analysis confirmed the LINC00152-related activation of oncogenic molecular pathways including those driven by PI3K/Akt, Ras, WNT, TP53, Notch and ErbB. Our results suggest that promoter hypomethylation related overexpression of LINC00152 can contribute to the pathogenesis of colorectal cancer by facilitating cell progression through the up-regulation of several oncogenic and metastasis promoting pathway elements.
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Affiliation(s)
- Orsolya Galamb
- 2nd Department of Internal Medicine, Semmelweis University, Szentkirályi str 46, 1088, Budapest, Hungary.
- MTA-SE Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.
| | - Alexandra Kalmár
- 2nd Department of Internal Medicine, Semmelweis University, Szentkirályi str 46, 1088, Budapest, Hungary
- MTA-SE Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary
| | - Anna Sebestyén
- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
| | - Titanilla Dankó
- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
| | - Csilla Kriston
- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
| | - István Fűri
- 2nd Department of Internal Medicine, Semmelweis University, Szentkirályi str 46, 1088, Budapest, Hungary
| | - Péter Hollósi
- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
| | - István Csabai
- Department of Physics of Complex Systems, Eötvös Loránd University, Budapest, Hungary
| | - Barnabás Wichmann
- 2nd Department of Internal Medicine, Semmelweis University, Szentkirályi str 46, 1088, Budapest, Hungary
- MTA-SE Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary
| | - Tibor Krenács
- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
| | - Barbara Kinga Barták
- 2nd Department of Internal Medicine, Semmelweis University, Szentkirályi str 46, 1088, Budapest, Hungary
| | - Zsófia Brigitta Nagy
- 2nd Department of Internal Medicine, Semmelweis University, Szentkirályi str 46, 1088, Budapest, Hungary
| | - Sára Zsigrai
- 2nd Department of Internal Medicine, Semmelweis University, Szentkirályi str 46, 1088, Budapest, Hungary
| | - Gábor Barna
- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
| | - Zsolt Tulassay
- MTA-SE Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary
| | - Péter Igaz
- 2nd Department of Internal Medicine, Semmelweis University, Szentkirályi str 46, 1088, Budapest, Hungary
- MTA-SE Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary
| | - Béla Molnár
- 2nd Department of Internal Medicine, Semmelweis University, Szentkirályi str 46, 1088, Budapest, Hungary
- MTA-SE Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary
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Li P, Zhang S, Mo Y, Zhang L, Wang Y, Xiong F, Zhang S, Liu J, Xu Y, Zeng Z, Xiong W, Li Y, Gong Z. Long non-coding RNA expression profiles and related regulatory networks in areca nut chewing-induced tongue squamous cell carcinoma. Oncol Lett 2020; 20:302. [PMID: 33093911 DOI: 10.3892/ol.2020.12165] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Accepted: 08/24/2020] [Indexed: 12/12/2022] Open
Abstract
Areca nut chewing is an important risk factor for developing tongue squamous cell carcinoma (TSCC), although the underlying molecular mechanism is unknown. To determine the potential molecular mechanisms of areca nut chewing-induced TSCC, the present study performed whole-genome detection with five pairs of TSCC and adjacent normal tissues, via mRNA- and long non-coding (lnc)RNA-gene chip analysis. A total of 3,860 differentially expressed genes were identified, including 2,193 lncRNAs and 1,667 mRNAs. Gene set-enrichment analysis revealed that the differentially expressed mRNAs were enriched in chromosome 22q13, 8p21 and 3p21 regions, and were regulated by nuclear factor kappa B (NF-κB) and interferon regulatory factors (IRFs). The results of ingenuity pathway analysis revealed that these mRNAs were significantly enriched for inflammatory immune-related signaling pathways. A co-expression network of mRNAs and lncRNAs was constructed by performing weighted gene co-expression network analysis. The present study focused on NF-κB-, IRF- and Th cell-signaling pathway-related lncRNAs and the corresponding mRNA-lncRNA regulatory networks. To the best of our knowledge, the present study was the first to investigate differential mRNA- and lncRNA-expression profiles in TSCCs induced by areca nut chewing. Inflammation-related mRNA-lncRNA regulatory networks driven by IRFs and NF-κB were identified, as well as the Th cell-related signaling pathways that play important carcinogenic roles in areca nut chewing-induced TSCC. These differentially expressed mRNAs and lncRNAs, and their regulatory networks provide insight for further analysis on the molecular mechanism of areca nut chewing-induced TSCC, candidate molecular markers and targets for further clinical intervention.
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Affiliation(s)
- Panchun Li
- Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China
| | - Shanshan Zhang
- Department of Stomatology, The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
| | - Yongzhen Mo
- NHC Key Laboratory of Carcinogenesis, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha, Hunan 410078, P.R. China
| | - Lishen Zhang
- NHC Key Laboratory of Carcinogenesis, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha, Hunan 410078, P.R. China
| | - Yumin Wang
- NHC Key Laboratory of Carcinogenesis, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha, Hunan 410078, P.R. China
| | - Fang Xiong
- Department of Stomatology, The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
| | - Shuai Zhang
- Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
| | - Jiang Liu
- Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China
| | - Yuming Xu
- Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China
| | - Zhaoyang Zeng
- NHC Key Laboratory of Carcinogenesis, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha, Hunan 410078, P.R. China
| | - Wei Xiong
- NHC Key Laboratory of Carcinogenesis, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha, Hunan 410078, P.R. China
| | - Yong Li
- Department of Medicine, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA
| | - Zhaojian Gong
- Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China
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30
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A System Biology-Based Approach for Designing Combination Therapy in Cancer Precision Medicine. BIOMED RESEARCH INTERNATIONAL 2020; 2020:5072697. [PMID: 32908895 PMCID: PMC7471815 DOI: 10.1155/2020/5072697] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 07/07/2020] [Accepted: 07/22/2020] [Indexed: 12/02/2022]
Abstract
In this paper, we have used an agent-based stochastic tumor growth model and presented a mathematical and theoretical perspective to cancer therapy. This perspective can be used to theoretical study of precision medicine and combination therapy in individuals. We have conducted a series of in silico combination therapy experiments. Based on cancer drugs and new findings of cancer biology, we hypothesize relationships between model parameters which in some cases represent individual genome characteristics and cancer drugs, i.e., in our approach, therapy players are delegated by biologically reasonable parameters. In silico experiments showed that combined therapies are more effective when players affect tumor via different mechanisms and have different physical dimensions. This research presents for the first time an algorithm as a theoretical viewpoint for the prediction of effectiveness and classification of therapy sets.
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31
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Zhang M, Chen Z, Zhang S, Wu L, Jie Y, Liao Y, Huang Y, Chen J, Shi B. Analysis of Differentially Expressed Long Non-coding RNAs and the Associated TF-mRNA Network in Tongue Squamous Cell Carcinoma. Front Oncol 2020; 10:1421. [PMID: 32923393 PMCID: PMC7456846 DOI: 10.3389/fonc.2020.01421] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Accepted: 07/06/2020] [Indexed: 12/15/2022] Open
Abstract
Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play crucial roles in tongue squamous cell carcinoma (TSCC) tumorigenesis. However, the comprehensive regulation of lncRNAs-transcription factors (TFs)-messenger RNAs (mRNAs) in TSCC remains largely unknown. The purpose of this study was to identify aberrantly expressed lncRNAs and the associated TF-mRNA network in TSCC. To explore lncRNA and mRNA expression profiles and their biological functions in TSCC, we surveyed the lncRNA and mRNA expression profiles of TSCC and adjacent tissues using next-generation RNA sequencing in six patients. Thousands of significantly differentially expressed lncRNAs (DELs) and mRNAs (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to demonstrate the principal functions of the significantly dysregulated lncRNAs and genes. A total of 40 DELs were screened between TSCC and adjacent non-cancerous tissues. Results obtained from GEPIA and StarBase confirmed the expression levels of nine pivotal DELs obtained in our study. Three of the nine deregulated DELs were identified to have a significant impact on the overall survival of TSCC patients, which were evaluated with GEPIA and StarBase. LncMAP was used to predict the lncRNA-TF-mRNA triplets in TSCC. Furthermore, based on these results, we established lncRNA-TF-mRNA coexpression networks for the up- and downregulated lncRNAs using Cytoscape. We also found that among the nine pivotal lncRNAs, there is limited research on the abnormally expressed lncRNAs, including RP11-54H7.4, CTD-2545M3.8, RP11-760H22.2, RP4-791M13.3, and LINC01405, in TSCC pathogenesis. This is the first study to show that RP11-54H7.4, LINC00152, and LINC01405 can be acted as a prognostic target for TSCC. Our findings provide a novel perspective and lay the foundation for future research on the potential roles of lncRNAs, TFs, and mRNAs in TSCC. Verification of the potential lncRNA-TF-mRNA regulatory networks will provide a more comprehensive understanding of the pathogenesis of TSCC.
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Affiliation(s)
- Mi Zhang
- School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China.,Fujian Key Laboratory of Oral Diseases, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China
| | - Zexi Chen
- Research Center of Dental and Craniofacial Implants, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China
| | - Sihui Zhang
- Research Center of Dental and Craniofacial Implants, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China
| | - Ling Wu
- Research Center of Dental and Craniofacial Implants, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China
| | - Yinghui Jie
- Research Center of Dental and Craniofacial Implants, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China
| | - Yunyang Liao
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Yue Huang
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Jiang Chen
- School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China.,Fujian Key Laboratory of Oral Diseases, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China
| | - Bin Shi
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
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He S, Wang X, Zhang J, Zhou F, Li L, Han X. TRG-AS1 is a potent driver of oncogenicity of tongue squamous cell carcinoma through microRNA-543/Yes-associated protein 1 axis regulation. Cell Cycle 2020; 19:1969-1982. [PMID: 32615889 PMCID: PMC7469544 DOI: 10.1080/15384101.2020.1786622] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
The long noncoding RNA T cell receptor gamma locus antisense RNA 1 (TRG-AS1) plays an important role in glioblastoma progression. The objective of this study was to determine the expression status of TRG-AS1 in tongue squamous cell carcinoma (TSCC). The regulatory effects of TRG-AS1 depletion on the malignant processes of TSCC cells were illustrated both in vitro and in vivo. Additionally, the precise molecular mechanisms through which TRG-AS promotes TSCC oncogenicity were investigated. TRG-AS1 expression in TSCC tissues and cell lines was detected using reverse transcription-quantitative PCR. Functional experiments including Cell Counting Kit-8 assay, flow cytometric apoptotic assay, migration and invasion assays, and xenograft tumor model analysis were conducted to severally determine the effects of TRG-AS1 on TSCC cell proliferation, apoptosis, migration, and invasion in vitro and tumor growth in vivo. Herein, TRG-AS1 was highly expressed in TSCC and closely associated with advanced TNM stage, high lymph node metastasis, and poor overall survival. Functionally, TRG-AS1 depletion suppressed TSCC cell proliferation, migration, and invasion in vitro; promoted cell apoptosis; and attenuated tumor growth in vivo. Mechanistically, TRG-AS1 served as a molecular sponge for microRNA-543 (miR-543), thereby contributing to the increased expression of Yes-associated protein 1 (YAP1) - a miR-543 target. Rescue experiments confirmed that miR-543 inhibition or YAP1 overexpression abrogated the anticancer effects of TRG-AS1 silencing in TSCC cells. In conclusion, TRG-AS1 aggravates TSCC malignancy by regulating the miR-543/YAP1 axis. Identification of the TRG-AS1/miR-543/YAP1 regulatory pathway may provide novel insights into TSCC diagnosis, prognosis, and therapy.
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Affiliation(s)
- Shuwei He
- Department of Nuclear Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
| | - Xu Wang
- Department of Nuclear Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
| | - Jingjing Zhang
- Department of Nuclear Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
| | - Fan Zhou
- Department of Nuclear Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
| | - Lei Li
- Department of Nuclear Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
| | - Xingmin Han
- Department of Nuclear Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China,CONTACT Xingmin Han
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Wang Y, Xin D, Zhou L. LncRNA LINC00152 Increases the Aggressiveness of Human Retinoblastoma and Enhances Carboplatin and Adriamycin Resistance by Regulating MiR-613/Yes-Associated Protein 1 (YAP1) Axis. Med Sci Monit 2020; 26:e920886. [PMID: 32541644 PMCID: PMC7315805 DOI: 10.12659/msm.920886] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Long noncoding RNA (lncRNA) acts as key regulator in human cancers, including retinoblastoma. However, the function of LINC00152 remains largely unknown in retinoblastoma. Thus, this study aimed to explore the role and molecular mechanisms of LINC00152 in retinoblastoma. MATERIAL AND METHODS The real-time quantitative polymerase chain reaction (RT-qPCR) was used to quantify the expression levels of LINC00152, miR-613 and yes-associated protein 1 (YAP1). The target genes of LINC00152 and miR-613 were identified by dual-luciferase reporter analysis, RNA immunoprecipitation (RIP) and RNA pulldown assays. The viability, apoptosis, and invasion of retinoblastoma cells were assessed by Cell Counting Kit-8, flow cytometry, and Transwell assays, respectively. In addition, western blot was used to test the protein expression in retinoblastoma cells or tissues. Cell sensitivity to carboplatin and adriamycin was analyzed by computing IC₅₀ value. The effects of LINC00152 silencing in vivo were measured by a xenograft experiment. RESULTS LINC00152 was obviously upregulated, while miR-613 was decreased in retinoblastoma tissues and cells. MiR-613, a target of LINC00152, was negatively regulated by LINC00152. Functional experiment further illustrated that silencing of LINC00152 evidently repressed proliferation, invasion, and autophagy while reinforced apoptosis of retinoblastoma cells, besides, retinoblastoma cells were more sensitive to carboplatin and adriamycin after knockdown of LINC00152. Importantly, knockdown of LINC00152-induced effects on retinoblastoma cells could be overturned by introducing miR-613 inhibitor. Downregulation of miR-613 abolished silencing of YAP1-effects on proliferation, apoptosis, invasion, autophagy, and chemoresistance of retinoblastoma cells. The results of the xenograft experiment indicated that LINC00152 silencing impeded tumor growth in vivo. CONCLUSIONS Mechanistically, LINC00152 enhanced the aggressiveness of retinoblastoma and boosted carboplatin and adriamycin resistance by regulating YAP1 by sponging miR-613 in human retinoblastoma.
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Affiliation(s)
- Ying Wang
- Department of Ophthalmology, Ningbo Eye Hospital, Ningbo, Zhejiang, China (mainland)
| | - Danli Xin
- Department of Ophthalmology, Ningbo Eye Hospital, Ningbo, Zhejiang, China (mainland)
| | - Lei Zhou
- Department of Ophthalmology, Ningbo Eye Hospital, Ningbo, Zhejiang, China (mainland)
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Liu X, Zhang B, Jia Y, Fu M. SNHG17 enhances the malignant characteristics of tongue squamous cell carcinoma by acting as a competing endogenous RNA on microRNA-876 and thereby increasing specificity protein 1 expression. Cell Cycle 2020; 19:711-725. [PMID: 32089063 PMCID: PMC7145335 DOI: 10.1080/15384101.2020.1727399] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 11/09/2019] [Accepted: 11/18/2019] [Indexed: 12/13/2022] Open
Abstract
A long noncoding RNA called SNHG17 (small nucleolar RNA host gene 17) is aberrantly expressed and plays essential roles in multiple human cancer types. Nevertheless, its expression pattern and specific functions in tongue squamous cell carcinoma (TSCC) have not been well studied until now. Hence, in this study, we aimed to measure SNHG17 expression in TSCC and to examine the actions of SNHG17 on the malignant characteristics of TSCC cells. The regulatory mechanism that mediates the oncogenic effects of SNHG17 on TSCC cells was investigated too. In this study, SNHG17 was found to be upregulated in TSCC, and this overexpression closely correlated with adverse clinical parameters and shorter overall survival among the patients with TSCC. The SNHG17 knockdown significantly decreased TSCC cell proliferation, migration, and invasion in vitro and tumor growth in vivo. Mechanism investigation revealed that SNHG17 acts as a competing endogenous RNA on microRNA-876 (miR-876) in TSCC cells. In addition, specificity protein 1 (SP1) was validated as a direct target gene of miR-876 in TSCC cells. SP1 expression restoration in TSCC cells reversed miR-876 overexpression-induced anticancer effects. MiR-876 downregulation strongly attenuated the actions of the SNHG17 knockdown in TSCC cells. SNHG17 plays an oncogenic part in TSCC cells both in vitro and in vivo via sponging of miR-876 and thereby upregulating SP1, which could be regarded as a promising target for TSCC therapy.
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Affiliation(s)
- Xiaoming Liu
- Institute of Oral Diseases, Oral Medicine Center, University of Chinese Academy of Sciences, Shenzhen Hospital, Shenzhen, Guangdong, P.R. China
| | - Baorong Zhang
- Institute of Oral Diseases, Oral Medicine Center, University of Chinese Academy of Sciences, Shenzhen Hospital, Shenzhen, Guangdong, P.R. China
| | - Yue Jia
- Institute of Oral Diseases, Oral Medicine Center, University of Chinese Academy of Sciences, Shenzhen Hospital, Shenzhen, Guangdong, P.R. China
| | - Ming Fu
- Institute of Oral Diseases, Oral Medicine Center, University of Chinese Academy of Sciences, Shenzhen Hospital, Shenzhen, Guangdong, P.R. China
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Ghafouri-Fard S, Mohammad-Rahimi H, Jazaeri M, Taheri M. Expression and function of long non-coding RNAs in head and neck squamous cell carcinoma. Exp Mol Pathol 2020; 112:104353. [DOI: 10.1016/j.yexmp.2019.104353] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Revised: 11/25/2019] [Accepted: 12/04/2019] [Indexed: 12/31/2022]
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36
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Rodríguez Zorrilla S, García García A, Blanco Carrión A, Gándara Vila P, Somoza Martín M, Gallas Torreira M, Pérez Sayans M. Exosomes in head and neck cancer. Updating and revisiting. J Enzyme Inhib Med Chem 2020; 34:1641-1651. [PMID: 31496355 PMCID: PMC6746279 DOI: 10.1080/14756366.2019.1662000] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Exosomes have gone from being considered simple containers of intracellular waste substances to be considered important carriers of cellular signals. Its broad capacity to promote tumour growth, both in situ and metastatic, has greatly intensified scientific research on them. In the same way and depending on its content, its tumour suppressive properties have opened a window of light and hope in the fight against cancer. In the present review we try to gather in a simple and understandable way the most relevant knowledge to date on the role of exosomes in oral squamous cell carcinoma, helping to understand their process of formation, release and activity on the tumour microenvironment.
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Affiliation(s)
- Samuel Rodríguez Zorrilla
- Oral Surgery and Implantology Unit, School of Medicine and Dentistry, University of Santiago de Compostela , Santiago de Compostela , Spain
| | - Abel García García
- Oral Surgery and Implantology Unit, School of Medicine and Dentistry, Instituto de Investigación Sanitaria de Santiago (IDIS) , Santiago de Compostela , Spain
| | - Andrés Blanco Carrión
- Oral Surgery and Implantology Unit, School of Medicine and Dentistry, University of Santiago de Compostela , Santiago de Compostela , Spain
| | - Pilar Gándara Vila
- Oral Surgery and Implantology Unit, School of Medicine and Dentistry, University of Santiago de Compostela , Santiago de Compostela , Spain
| | - Manuel Somoza Martín
- Oral Surgery and Implantology Unit, School of Medicine and Dentistry, University of Santiago de Compostela , Santiago de Compostela , Spain
| | - Mercedes Gallas Torreira
- Oral Surgery and Implantology Unit, School of Medicine and Dentistry, University of Santiago de Compostela , Santiago de Compostela , Spain
| | - Mario Pérez Sayans
- Oral Surgery and Implantology Unit, School of Medicine and Dentistry, Instituto de Investigación Sanitaria de Santiago (IDIS) , Santiago de Compostela , Spain
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Li X, Rui B, Cao Y, Gong X, Li H. Long non-coding RNA LINC00152 acts as a sponge of miRNA-193b-3p to promote tongue squamous cell carcinoma progression. Oncol Lett 2020; 19:2035-2042. [PMID: 32194700 DOI: 10.3892/ol.2020.11293] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2018] [Accepted: 07/26/2019] [Indexed: 12/29/2022] Open
Abstract
Dysregulated expression of long non-coding RNAs has been determined to be important in cancer development; however, their role in tongue squamous cell carcinoma (TSCC) progression and carcinogenesis, to the best of our knowledge, is yet to be elucidated. The present study revealed that long intergenic non-coding RNA 00152 (LINC00152) expression was significantly increased in human TSCC tissues compared with in tissues from matched controls using RT-qPCR. In TSCC cell lines, CAL-27 and SCC-9, LINC00152 was revealed to promote TSCC cell proliferation, enhance cell cycle progression and inhibit cell apoptosis. Additionally, migration and invasion of TSCC cell lines was increased in response to LINC00152 overexpression. Mechanistically, LINC00152 was determined to be localized in the cytoplasm and acted as a microRNA (miR)-193b-3p sponge, and LINC00152 knockdown or miR-193b-3p mimics both inhibited PI3K signaling pathway activation and downstream AKT phosphorylation; therefore, promoting TSCC progression in vitro. Overall, the results of the present study suggested that increased LINC00152 expression in TSCC tissues may act as a sponge of miR-193b-3p to promote cancer progression in vitro.
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Affiliation(s)
- Xiuhua Li
- Department of Stomatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.,School of Pharmacology, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China
| | - Bing Rui
- Department of Medical Microbiology and Parasitology, Second Military Medical University, Shanghai 200433, P.R. China
| | - Yongbing Cao
- School of Pharmacology, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China
| | - Xiaojian Gong
- School of Pharmacology, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China
| | - Hongjiao Li
- Department of Stomatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China
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Wang H, Liu Y, Tang A. Prognostic Values of Long Noncoding RNA linc00152 in Various Carcinomas: An Updated Systematic Review and Meta-Analysis. Oncologist 2020; 25:e31-e38. [PMID: 31801898 PMCID: PMC6964117 DOI: 10.1634/theoncologist.2018-0358] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Accepted: 11/21/2018] [Indexed: 12/23/2022] Open
Abstract
Dysregulation of the long noncoding RNA linc00152 has been reported in various solid tumors. Here, we performed a synthetic analysis to clarify the clinical value of linc00152 as a prognostic indicator in malignant tumors. Article collection was conducted using several electronic databases, including PubMed, Web of Science, Medline, OVID, and Embase (up to February 13, 2018). The meta-analysis comprised nine original studies and 808 total patients. The application of a random-effects model revealed significant positive association between high expression level of linc00152 and lymph node metastasis (odds ratio [OR] = 2.93, 95% confidence interval [CI]: 1.88-4.57, p < .0001; I2 = 48.8, p = .119) and negative association with low-grade cancer (OR = 2.43, 95% CI: 1.51-3.92; I2 = 61.7, p = .033), while with tumor recurrence (hazard ratio [HR] = 3.32, 95% CI: 1.98-5.57, p < .0001; I2 = 0, p = .451) by fixed-effects model as the low heterogeneity. As demonstrated via the application of the fixed-effects model, Linc00152 overexpression is positively related to poor overall survival (pooled HR = 1.98, 95% CI: 1.70-2.31, p < .0001; I2 = 0%, p = .756) and poor disease-free survival (HR = 1.66, 95% CI: 1.20-2.29, p < .0001; I2 = 75.8%, p = .042) in human solid cancers. Statistically significant associations were additionally found with cancer type, sample size, and follow-up time. In conclusion, linc00152 is of potential value as a novel biomarker of lymph node metastasis and prognosis in human cancer. IMPLICATIONS FOR PRACTICE: linc00152 is of potential value as a novel biomarker of lymph node metastasis and prognosis in human cancer.
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Affiliation(s)
- Han Wang
- Department of Urinary Surgery, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen UniversityShenzhenGuangdongPeople's Republic of China
| | - Yang Liu
- Department of Urinary Surgery, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen UniversityShenzhenGuangdongPeople's Republic of China
- Guangzhou Medical UniversityGuangzhouGuangdongPeople's Republic of China
| | - Aifa Tang
- Department of Urinary Surgery, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen UniversityShenzhenGuangdongPeople's Republic of China
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39
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Progress in the study of long noncoding RNA in tongue squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol 2020; 129:51-58. [DOI: 10.1016/j.oooo.2019.08.011] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Revised: 08/13/2019] [Accepted: 08/25/2019] [Indexed: 12/12/2022]
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40
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Fan C, Tang Y, Wang J, Wang Y, Xiong F, Zhang S, Li X, Xiang B, Wu X, Guo C, Ma J, Zhou M, Li X, Xiong W, Li Y, Li G, Zeng Z. Long non-coding RNA LOC284454 promotes migration and invasion of nasopharyngeal carcinoma via modulating the Rho/Rac signaling pathway. Carcinogenesis 2019; 40:380-391. [PMID: 30380023 DOI: 10.1093/carcin/bgy143] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Revised: 09/29/2018] [Accepted: 10/29/2018] [Indexed: 12/13/2022] Open
Abstract
Nasopharyngeal carcinoma (NPC) is a unique malignant cancer with high metastasis. Because the early symptoms of NPC patients are not obvious, most patients have distant metastases when diagnosed, which makes treatment difficult. Long non-coding RNAs (lncRNAs) are emerging as important regulators in human carcinogenesis. LncRNAs have been increasingly identified but remain largely unknown in NPC. Therefore, we performed gene expression profiling to screen for altered expression of lncRNAs in NPC tissues and adjacent samples. One lncRNA, LOC284454, was upregulated and associated with poor prognosis in NPC. In in vivo and in vitro assays, LOC284454 promoted the migration and invasion capacity of NPC cells. Mass spectrometry combined with bioinformatics suggested that LOC284454 affected the cytoskeletal and adhesion-related Rho/Rac signaling pathways. LOC284454 may be a potential novel treatment target and is expected to be a new diagnostic and prognostic marker in patients with NPC.
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Affiliation(s)
- Chunmei Fan
- The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital.,The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Science.,Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine
| | - Yanyan Tang
- The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital.,The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Science.,Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine
| | - Jinpeng Wang
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Science
| | - Yian Wang
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Science
| | - Fang Xiong
- The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital
| | - Shanshan Zhang
- The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital
| | - Xiayu Li
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Bo Xiang
- The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital.,The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Science.,Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine
| | - Xu Wu
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Science.,Department of Chemistry, University of North Dakota, Grand Forks, ND, USA
| | - Can Guo
- The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital.,The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Science
| | - Jian Ma
- The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital.,The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Science.,Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine
| | - Ming Zhou
- The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital.,The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Science.,Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine
| | - Xiaoling Li
- The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital.,The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Science.,Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine
| | - Wei Xiong
- The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital.,The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Science.,Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine
| | - Yong Li
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Science.,Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Guiyuan Li
- The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital.,The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Science.,Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine
| | - Zhaoyang Zeng
- The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital.,The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Science.,Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine
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Zheng Y, Zheng B, Meng X, Yan Y, He J, Liu Y. LncRNA DANCR promotes the proliferation, migration, and invasion of tongue squamous cell carcinoma cells through miR-135a-5p/KLF8 axis. Cancer Cell Int 2019; 19:302. [PMID: 31827393 PMCID: PMC6862788 DOI: 10.1186/s12935-019-1016-6] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Accepted: 11/04/2019] [Indexed: 12/15/2022] Open
Abstract
Background Tongue squamous cell carcinoma (TSCC) is a most invasive cancer with high mortality and poor prognosis. It is reported that lncRNA DANCR has implications in multiple types of cancers. However, its biological role and underlying mechanism in TSCC progress are not well elucidated. Methods Our present study first investigated the function of DANCR on the proliferation, migration and invasion of TSCC cells by silencing or overexpressing DANCR. Further, the miR-135a-5p-Kruppel-like Factor 8 (KLF8) axis was focused on to explore the regulatory mechanism of DANCR on TSCC cell malignant phenotypes. Xenografted tumor growth using nude mice was performed to examine the role of DANCR in vivo. Results DANCR knockdown reduced the viability and inhibited the migration and invasion of TSCC cells in vitro, while ectopic expression of DANCR induced opposite effects. In vivo, the tumor growth and the expression of matrix metalloproteinase (MMP)-2/9 and KLF8 were also blocked by DANCR inhibition. In addition, we found that miR-135-5p directly targeted DANCR, which was negatively correlated with DANCR on TSCC progression. Its inhibition reversed the beneficial effects of DANCR silence on TSCC malignancies. Furthermore, the expression of KLF8 evidently altered by both DANCR and miR-135a-5p. Silencing KLF8 using its specific siRNA showed that KLF8 was responsible for the induction of miR-135a-5p inhibitor on TSCC cell malignancies and MMP-2/9 expression. Conclusions These findings, for the first time, suggest that DANCR plays an oncogenic role in TSCC progression via targeting miR-135a-5p/KLF8 axis, which provides a promising biomarker and treatment approach for preventing TSCC.
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Affiliation(s)
- Ying Zheng
- 1Department of Orthodontics, School of Stomatology, China Medical University, 117 North Nanjing Street, Shenyang, 110002 People's Republic of China
| | - Bowen Zheng
- 1Department of Orthodontics, School of Stomatology, China Medical University, 117 North Nanjing Street, Shenyang, 110002 People's Republic of China
| | - Xue Meng
- 2Department of Stomatology, Shengjing Hospital of China Medical University, Shenyang, 110004 People's Republic of China
| | - Yuwen Yan
- 1Department of Orthodontics, School of Stomatology, China Medical University, 117 North Nanjing Street, Shenyang, 110002 People's Republic of China
| | - Jia He
- 1Department of Orthodontics, School of Stomatology, China Medical University, 117 North Nanjing Street, Shenyang, 110002 People's Republic of China
| | - Yi Liu
- 1Department of Orthodontics, School of Stomatology, China Medical University, 117 North Nanjing Street, Shenyang, 110002 People's Republic of China
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42
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Zha T, Su F, Liu X, Yang C, Liu L. Role of Long Non-Coding RNA (LncRNA) LINC-PINT Downregulation in Cardiomyopathy and Retinopathy Progression Among Patients with Type 2 Diabetes. Med Sci Monit 2019; 25:8509-8514. [PMID: 31711064 PMCID: PMC6873639 DOI: 10.12659/msm.918358] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background Despite the acknowledgement that LncRNA LINC-PINT may inhibit tumor cell invasion in human cancers, it is not yet determined when it comes to diabetes and its related complications. Material/Methods There were 244 patients with T2D and 126 healthy volunteers were admitted to People’s Hospital of Xinjiang Uygur Autonomous Region Hospital. Fasting blood (5 mL) was obtained from the patients and controls a day after admission. The diabetes patients’ fasting blood was extracted once every 6 months during follow-up. The total RNA was extracted and then used for detecting the expression of LINC-PINT. Results A comparison was made in this study, where LINC-PINT did not experience significant downregulation level in the majority of those suffering diabetes complications when in contrast to healthy controls, while LINC-PINT expression was found in diabetics. The follow-up study showed that LINC-PINT was downregulated in patients who developed cardiomyopathy and retinopathy or both but not in patients who developed other complications. Treatment with high glucose limited the extent of LINC-PINT expression in the ARPE-19 and AC16 cells. While the overexpression of LINC-PINT increased the viability of ARPE-19 and AC16 cells, siRNA-mediated silencing of LINC-PINT elicited the opposite effect. Conclusions Hence, we concluded that the overexpression of LINC-PINT may exhibit inhibitory effects on the progression of cardiomyopathy and retinopathy among patients with type 2 diabetes.
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Affiliation(s)
- Tianjian Zha
- Department of Burns, Wound Repair Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China (mainland)
| | - Fuzeng Su
- Department of Burns, Wound Repair Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China (mainland)
| | - Xiaolong Liu
- Department of Burns, Wound Repair Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China (mainland)
| | - Chunfeng Yang
- Department of Burns, Wound Repair Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China (mainland)
| | - Lihua Liu
- Department of Burns, Wound Repair Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China (mainland)
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43
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Abi A, Farahani N, Molavi G, Gheibi Hayat SM. Circular RNAs: epigenetic regulators in cancerous and noncancerous skin diseases. Cancer Gene Ther 2019; 27:280-293. [PMID: 31477805 DOI: 10.1038/s41417-019-0130-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2019] [Revised: 05/25/2019] [Accepted: 06/01/2019] [Indexed: 12/11/2022]
Abstract
The most frequent kind of malignancy in the universe is skin cancer, which has been categorized into non-melanoma and melanoma skin cancer. There are no complete information of the skin carcinogenesis process. A variety of external and internal agents contribute to the non-melanoma and melanoma skin cancer pathogenesis. These factors are epigenetic changes, X-rays, genetic, arsenic compounds, UV rays, and additional chemical products. It was found that there could be a relationship between the appearing novel and more suitable therapies for participants in this class of diseases and detection of basic molecular paths. A covalently closed loop structure bond connecting the 5' and 3' ends characterizes a new group of extensively expressed endogenous regulatory RNAs, which are called circular RNAs (circRNAs). Mammals commonly express circRNAs. They are of high importance in tumorigenesis. Multiple lines evidence indicated that a variety of circular RNAs are associated with initiation and development of skin-related diseases such as skin cancers. Given that different circular RNAs (hsa_circ_0025039, hsa_circRNA006612, circRNA005537, and circANRIL) via targeting various cellular and molecular targets (e.g., CDK4, DAB2IP, ZEB1, miR-889, and let-7c-3p) exert their effects on skin cancers progression. Herein, for first time, we summarized different circular RNAs in skin cancers and noncancerous diseases. Moreover, we highlighted crosstalk between circular RNAs and ceRNAs in cancerous conditions.
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Affiliation(s)
- Abbas Abi
- Department of Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Najmeh Farahani
- Department of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ghader Molavi
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Seyed Mohammad Gheibi Hayat
- Department of Medical Genetics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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Xu J, Guo J, Jiang Y, Liu Y, Liao K, Fu Z, Xiong Z. Improved characterization of the relationship between long intergenic non-coding RNA Linc00152 and the occurrence and development of malignancies. Cancer Med 2019; 8:4722-4731. [PMID: 31270960 PMCID: PMC6712457 DOI: 10.1002/cam4.2245] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2019] [Revised: 04/28/2019] [Accepted: 04/30/2019] [Indexed: 12/15/2022] Open
Abstract
Linc00152, located on chromosome 2p11.2, is a long intergenic non-coding RNA molecule with 828 nucleotides that is highly expressed in many types of human tumor tissues, especially in malignant tumors of the digestive system. Linc00152 promotes the occurrence and development of tumors by increasing tumor cell proliferation, invasion, metastasis, and apoptosis. Additionally, linc00152 contributes to the carcinogenesis of several cancers, including gastric cancer, liver cancer, hepatocellular carcinoma, gallbladder cancer, clear cell renal cell carcinoma, and colorectal cancer, by disturbing various signaling pathways (eg PI3K/AKT, mTOR, IL-1, and NOTCH 1 signaling pathways). High linc00152 expression levels are associated with chemoresistance as well as poor prognosis and shorter survival. Continual advances made in the relevant research have indicated that linc00152 may be useful as a new tumor molecular biomarker, applicable for tumor diagnosis, targeted therapy, and prognosis assessment. This review summarizes the progress in the research into the relationship between linc00152 and the occurrence and development of malignancies based on molecular functions, regulatory mechanisms, and clinical applications.
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Affiliation(s)
- Jiasheng Xu
- Department of Pathology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Jingjing Guo
- Department of Pathology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yangkai Jiang
- Department of Pathology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yujun Liu
- Queen Mary College of Nanchang University, Nanchang, China
| | - Kaili Liao
- Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Zhonghua Fu
- Department of Burns, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Zhenfang Xiong
- Department of Pathology, The First Affiliated Hospital of Nanchang University, Nanchang, China
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45
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Fan C, Tu C, Qi P, Guo C, Xiang B, Zhou M, Li X, Wu X, Li X, Li G, Xiong W, Zeng Z. GPC6 Promotes Cell Proliferation, Migration, and Invasion in Nasopharyngeal Carcinoma. J Cancer 2019; 10:3926-3932. [PMID: 31417636 PMCID: PMC6692608 DOI: 10.7150/jca.31345] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Accepted: 05/07/2019] [Indexed: 12/14/2022] Open
Abstract
Nasopharyngeal carcinoma (NPC) is a highly metastatic tumor that occurs frequently in Southeast Asia, particularly including southern China. Epstein-Barr virus infection is well established as a primary cause of NPC; nevertheless, the mechanisms underlying NPC pathogenesis remain largely unknown. In our previous study, we conducted whole-genome sequencing to screen for genomic variations that were associated with NPC. Of the resultantly identified variations, glypican-6 (GPC6), was shown, for the first time, to be frequently mutated in NPC. In the present study, we verified this finding and conducted a series of functional experiments, which demonstrated that GPC6 promotes the migration, invasion, and proliferation of NPC cells in vitro. Thus, the present study identified novel biological functions for GPC6 in NPC, and thus, showed that GPC6 may be a promising potential therapeutic target for this disease.
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Affiliation(s)
- Chunmei Fan
- NHC Key Laboratory of Carcinogenesis (Central South University) and Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and Basic Medical Science, Central South University, Changsha, Hunan, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Chaofeng Tu
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and Basic Medical Science, Central South University, Changsha, Hunan, China
| | - Peng Qi
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and Basic Medical Science, Central South University, Changsha, Hunan, China
| | - Can Guo
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and Basic Medical Science, Central South University, Changsha, Hunan, China
| | - Bo Xiang
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and Basic Medical Science, Central South University, Changsha, Hunan, China
| | - Ming Zhou
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and Basic Medical Science, Central South University, Changsha, Hunan, China
| | - Xiayu Li
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and Basic Medical Science, Central South University, Changsha, Hunan, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Xu Wu
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and Basic Medical Science, Central South University, Changsha, Hunan, China
- Department of Chemistry, University of North Dakota, Grand Forks, North Dakota, USA
| | - Xiaoling Li
- NHC Key Laboratory of Carcinogenesis (Central South University) and Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and Basic Medical Science, Central South University, Changsha, Hunan, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Guiyuan Li
- NHC Key Laboratory of Carcinogenesis (Central South University) and Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and Basic Medical Science, Central South University, Changsha, Hunan, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Wei Xiong
- NHC Key Laboratory of Carcinogenesis (Central South University) and Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and Basic Medical Science, Central South University, Changsha, Hunan, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Zhaoyang Zeng
- NHC Key Laboratory of Carcinogenesis (Central South University) and Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and Basic Medical Science, Central South University, Changsha, Hunan, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
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Li J, Li Y, Wu X, Li Y. Identification and validation of potential long non-coding RNA biomarkers in predicting survival of patients with head and neck squamous cell carcinoma. Oncol Lett 2019; 17:5642-5652. [PMID: 31186787 PMCID: PMC6507327 DOI: 10.3892/ol.2019.10261] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Accepted: 03/21/2019] [Indexed: 12/31/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) are frequently dysregulated in cancer and their aberrant expression has been associated with cancer diagnosis and prognosis, which suggests that they may be promising molecular biomarkers. However, understanding of the expression pattern of lncRNAs and their prognostic roles in head and neck squamous cell carcinoma (HNSCC) is relatively limited. In the current study, the prognostic value of lncRNA expression profiles in predicting the OS of patients with HNSCC was investigated by integrating clinical and profiling data from The Cancer Genome Atlas. A total of ten lncRNAs closely associated with the prognosis of patients with HNSCC were identified and may serve as novel biomarkers. This 10-lncRNA signature was used to classify patients into 2 groups with significantly different overall survival (OS) times (median OS time, 1.65 vs. 13.04 years; P<0.0001). This lncRNA signature was validated in an independent testing cohort. The results of multivariable Cox regression and stratification analyses revealed that the prognostic value of the 10-lncRNA signature was independent of other clinical and pathological factors for the survival of patients with HNSCC. Functional analysis demonstrated that lncRNA expression-based risk scoring may reflect the basic status of the immune response in the tumor microenvironment. The presented study demonstrated the value of a lncRNA signature as a potential biomarker to improve the clinical prognosis of patients with HNSCC.
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Affiliation(s)
- Junyu Li
- Department of Radiotherapy, Cancer Hospital of Jiangxi Province, Nanchang, Jiangxi 330029, P.R. China
| | - Yuehua Li
- Department of Medical Oncology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China
| | - Xiaoping Wu
- Department of Medical Oncology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China
| | - Ying Li
- Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan, Hubei 430079, P.R. China
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Chen X, Yu J, Tian H, Shan Z, Liu W, Pan Z, Ren J. Circle RNA hsa_circRNA_100290 serves as a ceRNA for miR-378a to regulate oral squamous cell carcinoma cells growth via Glucose transporter-1 (GLUT1) and glycolysis. J Cell Physiol 2019; 234:19130-19140. [PMID: 31187488 DOI: 10.1002/jcp.28692] [Citation(s) in RCA: 93] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Revised: 02/20/2019] [Accepted: 03/21/2019] [Indexed: 12/30/2022]
Abstract
Aerobic glycolysis (the Warburg effect) is a robust metabolic hallmark of most tumors, including oral squamous cell carcinoma (OSCC). Glucose transporter 1 (GLUT1), a major glucose transporter regulating the glucose uptake, is upregulated in OSCC and participated in the cell glycolysis of OSCC. The deregulation and function of noncoding RNAs in cancers have been widely reported. Reportedly, hsa_circular RNA (circRNA)_100290 (circ_SLC30A7) is significantly upregulated (fold change = 6.91, p < 0.0000001) in OSCC. According to online tools prediction (miRWalk, miRanda, and Targetscan), miR-378a could simultaneously target circRNA_100290 and GLUT1. Herein, the expression of circRNA_100290 and GLUT1 remarkably increased in oral tumor tissue specimens and cells. In OSCC cell lines, cell proliferation and glycolysis could be remarkably downregulated by circRNA_100290 silence, which could be rescued by GLUT1 overexpression. Conversely, miR-378a expression could be remarkably inhibited in tumor tissue specimens and cells. The effect of miR-378a overexpression on OSCC cells was similar to those of circRNA_100290 silence. miR-378a directly bound to circRNA_100290 and GLUT1 3'-untranslated region, circRNA_100290 could remarkably relieve miR-378a-induced inhibition on GLUT1 via acting as a competing endogenous RNA (ceRNA). miR-378a inhibition remarkably attenuated the effect of circRNA_100290 silence on cell proliferation and glycolysis in OSCC cell lines. In summary, circRNA_100290 serves as a ceRNA to counteract miR-378a-mediated GLUT1 suppression, thus promoting glycolysis and cell proliferation in OSCC. We provide a reliable experimental basis for understanding the mechanism of cell growth and glycolysis deregulation in OSCC.
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Affiliation(s)
- Xing Chen
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.,Department of Head and Neck Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Jianjun Yu
- Department of Head and Neck Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Hao Tian
- Department of Head and Neck Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Zhenfeng Shan
- Department of Head and Neck Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Wei Liu
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Zhen Pan
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Jihao Ren
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
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Pentenero M, Bowers LM, Jayasinghe R, Yap T, Cheong SC, Kerr AR, Farah CS, Alevizos I. World Workshop on Oral Medicine VII: Clinical evidence of differential expression of lncRNAs in oral squamous cell carcinoma: A scoping review. Oral Dis 2019; 25 Suppl 1:88-101. [PMID: 31140697 PMCID: PMC6544174 DOI: 10.1111/odi.13076] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2019] [Revised: 02/08/2019] [Accepted: 02/22/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Long non-coding RNAs (lncRNAs) have important roles in regulating gene expression pertaining to cell proliferation, survival, migration and genomic stability. Dysregulated expression of lncRNAs is implicated in cancer initiation, progression and metastasis. OBJECTIVES To explore, map and summarize the extent of evidence from clinical studies investigating the differential expression of lncRNAs in oral/tongue squamous cell carcinoma. METHODS PubMed, Scopus and Web of Science were used as search engines. Clinical, full-length, English language studies were included. PRISMA-ScR protocol was used to evaluate and present results. The present scoping review summarizes relationships of the differential expression of lncRNAs with the presence of tumour and with clinicopathological features including survival. RESULTS Almost half of the investigated transcripts have been explored in more than one study, yet not always with consistent results. The collected data were also compared to the limited studies investigating oral epithelial dysplasia. Data are not easily comparable, first because of different methods used to define what differential expression is, and second because only a limited number of studies performed multivariate analyses to identify clinicopathological features associated with the differentially expressed lncRNAs. CONCLUSIONS Standard methods and more appropriate data analyses are needed in order to achieve reliable results from future studies.
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Affiliation(s)
- Monica Pentenero
- Department of Oncology, Oral Medicine and Oral Oncology Unit, University of Turin, Turin, Italy
| | - Leah M Bowers
- Department of Stomatology, Division of Oral Medicine, Medical University of South Carolina, Charleston, SC, USA
| | - Ruwan Jayasinghe
- Department of Oral Medicine and Periodontology, Faculty of Dental Sciences, University of Peradeniya, Peradeniya, Sri Lanka
| | - Tami Yap
- Melbourne Dental School, University of Melbourne, Melbourne, Victoria, Australia
| | - Sok Ching Cheong
- Head and Neck Cancer Research Team, Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia
| | | | - Camile S Farah
- Australian Centre for Oral Oncology Research & Education, UWA Dental School, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia
| | - Ilias Alevizos
- Sjogren's Syndrome and Salivary Gland Dysfunction Unit, NIDCR/NIH, Bethesda, MD, USA
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49
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Zhang L, Meng X, Zhu XW, Yang DC, Chen R, Jiang Y, Xu T. Long non-coding RNAs in Oral squamous cell carcinoma: biologic function, mechanisms and clinical implications. Mol Cancer 2019; 18:102. [PMID: 31133028 PMCID: PMC6535863 DOI: 10.1186/s12943-019-1021-3] [Citation(s) in RCA: 114] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2019] [Accepted: 04/22/2019] [Indexed: 01/17/2023] Open
Abstract
There is growing evidence that regions of the genome that cannot encode proteins play an important role in diseases. These regions are usually transcribed into long non-coding RNAs (lncRNAs). LncRNAs, little or no coding potential, are defined as capped transcripts longer than 200 nucleotides. New sequencing technologies have shown that a large number of aberrantly expressed lncRNAs are associated with multiple cancer types and indicated they have emerged as an important class of pervasive genes during the development and progression of cancer. However, the underlying mechanism in cancer is still unknown. Therefore, it is necessary to elucidate the lncRNA function. Notably, many lncRNAs dysregulation are associated with Oral squamous cell carcinoma (OSCC) and affect various aspects of cellular homeostasis, including proliferation, survival, migration or genomic stability. This review expounds the up- or down-regulation of lncRNAs in OSCC and the molecular mechanisms by which lncRNAs perform their function in the malignant cell. Finally, the potential of lncRNAs as non-invasive biomarkers for OSCC diagnosis are also described. LncRNAs hold promise as prospective novel therapeutic targets, but more research is needed to gain a better understanding of their biologic function.
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Affiliation(s)
- Lei Zhang
- College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei, 230032, China.,Department of Periodontology, College and Hospital of Stomatology, Anhui Medical University, Hefei, 230032, Anhui Province, China
| | - Xiang Meng
- School of Stomatology, Anhui Medical University, Hefei, 230032, Anhui Province, China
| | - Xin-Wei Zhu
- College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei, 230032, China.,Outpatient Department of Binhu District, College and Hospital of Stomatology, Anhui Medical University, Hefei, 230601, Anhui Province, China
| | - Deng-Cheng Yang
- School of Stomatology, Anhui Medical University, Hefei, 230032, Anhui Province, China
| | - Ran Chen
- School of Stomatology, Anhui Medical University, Hefei, 230032, Anhui Province, China
| | - Yong Jiang
- Department of Stomatology, The Fourth Affiliated Hospital of Anhui Medical University, 372 Tunxi Road, Hefei, 230000, Anhui Province, China.
| | - Tao Xu
- School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui Province, China. .,Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui Province, China.
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50
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Fan CM, Wang JP, Tang YY, Zhao J, He SY, Xiong F, Guo C, Xiang B, Zhou M, Li XL, Li Y, Li GY, Xiong W, Zeng ZY. circMAN1A2 could serve as a novel serum biomarker for malignant tumors. Cancer Sci 2019; 110:2180-2188. [PMID: 31046163 PMCID: PMC6609809 DOI: 10.1111/cas.14034] [Citation(s) in RCA: 88] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Revised: 04/24/2019] [Accepted: 04/27/2019] [Indexed: 12/13/2022] Open
Abstract
Novel diagnostic and prognostic biomarkers of cancers are needed to improve precision medicine. Circular RNAs act as important regulators in cancers at the transcriptional and posttranscriptional levels. The circular RNA circMAN1A2 is highly expressed in nasopharyngeal carcinoma according to our previous RNA sequencing data; however, the expression and functions of circMAN1A2 in cancers are still obscure. Therefore, in this study, we evaluated the expression of circMAN1A2 in the sera of patients with nasopharyngeal carcinoma and other malignant tumors and analyzed its correlations with clinical features and diagnostic values. The expression levels of circMAN1A2 were detected by quantitative real-time PCR, and the correlations of clinical features with circMAN1A2 expression were analyzed by χ2 tests. Receiver operating characteristic curves were used to evaluate the clinical applications of circMAN1A2. The results showed that circMAN1A2 was upregulated in nasopharyngeal carcinoma, oral cancer, thyroid cancer, ovarian cancer, and lung cancer, with areas under the curves of 0.911, 0.779, 0.734, 0.694, and 0.645, respectively, indicating the good diagnostic value of circMAN1A2. Overall, our findings suggested that circMAN1A2 could be a serum biomarker for malignant tumors, providing important insights into diagnostic approaches for malignant tumors. Further studies are needed to elucidate the mechanisms of circMAN1A2 in the pathogenesis of cancer.
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Affiliation(s)
- Chun-Mei Fan
- NHC Key Laboratory of Carcinogenesis, Xiangya Hospital, Central South University, Changsha, China.,The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China.,Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Jin-Peng Wang
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Yan-Yan Tang
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Jin Zhao
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Shu-Yi He
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Fang Xiong
- NHC Key Laboratory of Carcinogenesis, Xiangya Hospital, Central South University, Changsha, China
| | - Can Guo
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Bo Xiang
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Ming Zhou
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Xiao-Ling Li
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
| | - Yong Li
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China.,Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Gui-Yuan Li
- NHC Key Laboratory of Carcinogenesis, Xiangya Hospital, Central South University, Changsha, China.,The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China.,Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Wei Xiong
- NHC Key Laboratory of Carcinogenesis, Xiangya Hospital, Central South University, Changsha, China.,The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China.,Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Zhao-Yang Zeng
- NHC Key Laboratory of Carcinogenesis, Xiangya Hospital, Central South University, Changsha, China.,The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China.,Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, China
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