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Yang P, Gu H, Wu X, Chen G, Liu H, Chen Z. Tumour protein p53-activated lncRNA PGM5-AS1 suppresses lung cancer growth and stemness by targeting R-spondin1 via microRNA-1247-5p. Arch Physiol Biochem 2025:1-13. [PMID: 40035308 DOI: 10.1080/13813455.2025.2459318] [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: 06/20/2024] [Revised: 11/06/2024] [Accepted: 01/22/2025] [Indexed: 03/05/2025]
Abstract
OBJECTIVE This study was to investigated the inhibitory role of the tumour protein p53 (TP53)-activated PGM5-AS1 in lung cancer (LC) cell proliferation, invasion, and CSC-like properties and its underlying mechanisms. METHODS The effect of PGM5-AS1 on LC cell development was determined. Stem cell markers, aldehyde dehydrogenase activity in cells were tested, as well as the ability of stem cells to form spheroids. The interaction of PGM5-AS1 and TP53 was determined. The binding link of PGM5-AS1, miR-1247-5p, and R-spondin1 (RSPO1) was verified. RESULTS PGM5-AS1 was elevated by a combination of TP53 and PGM5-AS1 promoters. PGM5-AS1 was a molecular sponge of miR-1247-5p in LC cells, and miR-1247-5p targeted RSPO1. Elevating PGM5-AS1 or repressing miR-1247-5p restrained LC cell growth and stemness, which were reversed by depression of RSPO1. CONCLUSION This study conveys that TP53-elevated PGM5-AS1 mediates miR-1247-5p to target RSPO1, thereby inhibiting LC growth and stemness, representing a novel avenue for LC therapy.
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Affiliation(s)
- Peng Yang
- Department of Cardiothoracic and Vascular Surgery, Shenzhen Guangming District People's Hospital, Shenzhen, Guangdong, China
| | - Hong Gu
- Department of Cardiothoracic and Vascular Surgery, Shenzhen Guangming District People's Hospital, Shenzhen, Guangdong, China
| | - Xuanqin Wu
- Department of Cardiothoracic and Vascular Surgery, Shenzhen Guangming District People's Hospital, Shenzhen, Guangdong, China
| | - Geng Chen
- Department of Cardiothoracic and Vascular Surgery, Shenzhen Guangming District People's Hospital, Shenzhen, Guangdong, China
| | - Heng Liu
- Department of Cardiothoracic and Vascular Surgery, Shenzhen Guangming District People's Hospital, Shenzhen, Guangdong, China
| | - Zhongliang Chen
- Department of Cardiothoracic and Vascular Surgery, Shenzhen Guangming District People's Hospital, Shenzhen, Guangdong, China
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Wang J, Ye J, Dang Y, Xu S. LncRNA PGM5-AS1 inhibits non-small cell lung cancer progression by targeting miRNA-423-5p/SLIT2 axis. Cancer Cell Int 2024; 24:216. [PMID: 38902704 PMCID: PMC11191156 DOI: 10.1186/s12935-024-03402-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Accepted: 06/09/2024] [Indexed: 06/22/2024] Open
Abstract
Non-small cell lung cancer (NSCLC) is a common and aggressive primary malignancy worldwide. Dysregulation of long non-coding RNAs (lncRNAs) has been shown to play an essential regulatory role in multiple cancers. However, the role of PGM5-AS1 in NSCLC remains unclear. Here, we found that PGM5-AS1 was down-regulated in NSCLC tissues and cells. Furthermore, reduced PGM5-AS1 expression levels were associated with larger tumor size, positive lymph node metastasis, advanced TNM stage and worse prognosis. We found that overexpression of PGM5-AS1 inhibited cell proliferation and metastasis, and induced apoptosis and G0/G1 cell cycle arrest in NSCLC cell lines. Using dual luciferase gene reporter and RNA immunoprecipitation assays, we confirmed that miR-423-5p interacted with PGM5-AS1, and that their expression levels were negatively correlated in NSCLC tissues. miR-423-5p was also found to reverse PGM5-AS1-induced malignant biological behavior. Moreover, we identified slit guidance ligand 2 (SLIT2) as a target gene of miR-423-5p. Using a dual luciferase gene reporter assay, we confirmed the regulatory relationship between SLIT2 and miR-423-5p and demonstrated that their expression levels were negatively correlated. Our rescue experiments showed that SLIT2 knockdown reversed miR-423-5p-mediated effects. Overall, this study identifies PGM5-AS1 as a potential prognostic biomarker for NSCLC and shows that PGM5-AS1 suppresses NSCLC development by regulating the miR-423-5p/SLIT2 axis.
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Affiliation(s)
- Jiajun Wang
- Department of Thoracic Surgery, The First Hospital of China Medical University, No. 155, North Nanjing Street, Shenyang, 110001, Liaoning, China
| | - Jun Ye
- Department of Thoracic Surgery, The First Hospital of China Medical University, No. 155, North Nanjing Street, Shenyang, 110001, Liaoning, China
| | - Yuxue Dang
- Department of Radiology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Shenyang, 110004, China
| | - Shun Xu
- Department of Thoracic Surgery, The First Hospital of China Medical University, No. 155, North Nanjing Street, Shenyang, 110001, Liaoning, China.
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3
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Zhou M, Bao S, Gong T, Wang Q, Sun J, Li J, Lu M, Sun W, Su J, Chen H, Liu Z. The transcriptional landscape and diagnostic potential of long non-coding RNAs in esophageal squamous cell carcinoma. Nat Commun 2023; 14:3799. [PMID: 37365153 PMCID: PMC10293239 DOI: 10.1038/s41467-023-39530-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 06/14/2023] [Indexed: 06/28/2023] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is a deadly cancer with no clinically relevant biomarkers for early detection. Here, we comprehensively characterized the transcriptional landscape of long non-coding RNAs (lncRNAs) in paired tumor and normal tissue specimens from 93 ESCC patients, and identified six key malignancy-specific lncRNAs that were integrated into a Multi-LncRNA Malignancy Risk Probability model (MLMRPscore). The MLMRPscore performed robustly in distinguishing ESCC from normal controls in multiple in-house and external multicenter validation cohorts, including early-stage I/II cancer. In addition, five candidate lncRNAs were confirmed to have non-invasive diagnostic potential in our institute plasma cohort, showing superior or comparable diagnostic accuracy to current clinical serological markers. Overall, this study highlights the profound and robust dysregulation of lncRNAs in ESCC and demonstrates the potential of lncRNAs as non-invasive biomarkers for the early detection of ESCC.
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Affiliation(s)
- Meng Zhou
- School of Biomedical Engineering, Eye Hospital, Wenzhou Medical University, 325027, Wenzhou, P. R. China
| | - Siqi Bao
- School of Biomedical Engineering, Eye Hospital, Wenzhou Medical University, 325027, Wenzhou, P. R. China
| | - Tongyang Gong
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, P. R. China
| | - Qiang Wang
- Department of Anesthesiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, P. R. China
| | - Jie Sun
- School of Biomedical Engineering, Eye Hospital, Wenzhou Medical University, 325027, Wenzhou, P. R. China
| | - Jiaqi Li
- School of Biomedical Engineering, Eye Hospital, Wenzhou Medical University, 325027, Wenzhou, P. R. China
| | - Minyi Lu
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, P. R. China
| | - Wanyuan Sun
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, P. R. China
| | - Jianzhong Su
- School of Biomedical Engineering, Eye Hospital, Wenzhou Medical University, 325027, Wenzhou, P. R. China.
| | - Hongyan Chen
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, P. R. China.
- Key Laboratory of Cancer and Microbiome, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, P. R. China.
| | - Zhihua Liu
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, P. R. China.
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Zhao L, Yu L, Wang X, He J, Zhu X, Zhang R, Yang A. Mechanisms of function and clinical potential of exosomes in esophageal squamous cell carcinoma. Cancer Lett 2023; 553:215993. [PMID: 36328162 DOI: 10.1016/j.canlet.2022.215993] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 10/05/2022] [Accepted: 10/27/2022] [Indexed: 11/20/2022]
Abstract
Esophageal squamous cell carcinoma (ESCC) remains one of the most lethal and widespread malignancies in China. Exosomes, a subset of tiny extracellular vesicles manufactured by all cells and present in all body fluids, contribute to intercellular communication and have become a focus of the search for new therapeutic strategies for cancer. A number of global analyses of exosome-mediated functions and regulatory mechanism in malignant diseases have recently been reported. There is extensive evidence that exosomes can be used as diagnostic and prognostic markers for cancer. However, our understanding of their clinical value and mechanisms of action in ESCC is still limited and has not been systematically reviewed. Here, we review current research specifically focused on the functions and mechanisms of action of ESCC tumor-derived exosomes and non-ESCC-derived exosomes in ESCC progression and describe opportunities and challenges in the clinical translation of exosomes.
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Affiliation(s)
- Lijun Zhao
- Henan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, Henan, China
| | - Lili Yu
- Henan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, Henan, China
| | - Xiangpeng Wang
- Henan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, Henan, China
| | - Jangtao He
- Henan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, Henan, China
| | - Xiaofei Zhu
- Henan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, Henan, China.
| | - Rui Zhang
- The State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, China.
| | - Angang Yang
- Henan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, Henan, China; The State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, China.
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Han Y, Zhao G, Shi X, Wang Y, Wen X, Zhang L, Guo X. The Emerging Role of Long Non-Coding RNAs in Esophageal Cancer: Functions in Tumorigenesis and Clinical Implications. Front Pharmacol 2022; 13:885075. [PMID: 35645836 PMCID: PMC9137892 DOI: 10.3389/fphar.2022.885075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Accepted: 04/12/2022] [Indexed: 11/17/2022] Open
Abstract
Esophageal cancer (EC) is one of the most common malignancies of digestive tracts with poor five-year survival rate. Hence, it is very significant to further investigate the occurrence and development mechanism of esophageal cancer, find more effective biomarkers and promote early diagnosis and effective treatment. Long non-coding RNAs (lncRNAs) are generally defined as non-protein-coding RNAs with more than 200 nucleotides in length. Existing researches have shown that lncRNAs could act as sponges, guides, scaffolds, and signal molecules to influence the oncogene or tumor suppressor expressions at transcriptional, post-transcriptional, and protein levels in crucial cellular processes. Currently, the dysregulated lncRNAs are reported to involve in the pathogenesis and progression of EC. Importantly, targeting EC-related lncRNAs through genome editing, RNA interference and molecule drugs may be one of the most potential therapeutic methods for the future EC treatment. In this review, we summarized the biological functions and molecular mechanisms of lncRNAs, including oncogenic lncRNAs and tumor suppressor lncRNAs in EC. In addition, we generalized the excellent potential lncRNA candidates for diagnosis, prognosis and therapy in EC. Finally, we discussed the current challenges and opportunities of lncRNAs for EC.
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Affiliation(s)
- Yali Han
- Departments of Physiology, Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Academy for Advanced Interdisciplinary Studies, Henan University, Kaifeng, China
| | - Guo Zhao
- Department of Preventive Medicine, Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Academy for Advanced Interdisciplinary Studies, Henan University, Kaifeng, China
| | - Xinhang Shi
- Department of Preventive Medicine, Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Academy for Advanced Interdisciplinary Studies, Henan University, Kaifeng, China
| | - Yushan Wang
- Departments of Physiology, Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Academy for Advanced Interdisciplinary Studies, Henan University, Kaifeng, China
| | - Xin Wen
- Department of Preventive Medicine, Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Academy for Advanced Interdisciplinary Studies, Henan University, Kaifeng, China
| | - Lu Zhang
- Department of Preventive Medicine, Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Academy for Advanced Interdisciplinary Studies, Henan University, Kaifeng, China
| | - Xiangqian Guo
- Department of Preventive Medicine, Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Academy for Advanced Interdisciplinary Studies, Henan University, Kaifeng, China
- *Correspondence: Xiangqian Guo,
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Su X, Xue C, Xie C, Si X, Xu J, Huang W, Huang Z, Lin J, Chen Z. lncRNA-LET Regulates Glycolysis and Glutamine Decomposition of Esophageal Squamous Cell Carcinoma Through miR-93-5p/miR-106b-5p/SOCS4. Front Oncol 2022; 12:897751. [PMID: 35619921 PMCID: PMC9127425 DOI: 10.3389/fonc.2022.897751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 04/04/2022] [Indexed: 11/13/2022] Open
Abstract
Background Dysregulated non-coding RNAs exhibit critical functions in various cancers. Nonetheless, the levels and corresponding functions of cirCSNX14 in esophageal squamous cell carcinoma (ESCC) yet remain to be elucidated. Methods Initially, the aberrant low levels of lncRNA-LET within ESCC tissues are validated via qRT-PCR observations. Moreover, the effects of lncRNA-LET upregulation on cell proliferation in vitro are determined. In addition, a series of assays determining the mechanistic views related to metabolism is conducted. Furthermore, the effects of lncRNA-LET in affecting tumor growth are investigated in vivo in a mouse model. Moreover, the interactions between lncRNA-LET and its networks are predicted and determined by RNA immunoprecipitation-assisted qRT-PCR as well as luciferase reporter assays. Results The downregulation of lncRNA-LET is correlated to the poor prognosis of ESCC patients. Moreover, the upregulated expression of lncRNA-LET could have reduced the cell viability. In vivo tumor inhibition efficacy assays showed that an increase of lncRNA-LET presented excellent inhibitory effects on cancer proliferation as reflected by tumor weight and volume in mice. Finally, the mechanistic views regarding the effects of miR-106b-5p or miR-93-5p and SOCS4 on ESCC are related to the feedback of lncRNA-LET. Conclusion Collectively, this study suggested that lncRNA-LET miR-93-5p or the miR-106b-5p-SOCS4 axis may provide great potential in establishing ESCC therapy.
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Affiliation(s)
- Xincheng Su
- Department of Gastrointestinal and Esophageal Surgery, The 2nd Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Cong Xue
- Department of Gastrointestinal and Esophageal Surgery, The 2nd Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Chengke Xie
- Department of Gastrointestinal and Esophageal Surgery, The 2nd Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Xianzhe Si
- Department of Gastrointestinal and Esophageal Surgery, The 2nd Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Jie Xu
- Department of Gastrointestinal and Esophageal Surgery, The 2nd Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Wenbo Huang
- Department of Gastrointestinal and Esophageal Surgery, The 2nd Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Zhijun Huang
- Department of Gastrointestinal and Esophageal Surgery, The 2nd Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Jianqing Lin
- Department of Oncology, The 2nd Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Zhiyao Chen
- Department of Gastrointestinal and Esophageal Surgery, The 2nd Affiliated Hospital of Fujian Medical University, Quanzhou, China
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7
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Qiao G, Zhang W, Dong K. Regulation of ferroptosis by noncoding RNAs: a novel promise treatment in esophageal squamous cell carcinoma. Mol Cell Biochem 2022; 477:2193-2202. [PMID: 35449482 DOI: 10.1007/s11010-022-04441-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 04/08/2022] [Indexed: 02/08/2023]
Abstract
Esophageal squamous cell carcinoma (ESCC) is a highly prevalent tumor that requires extensive research. Ferroptosis is a unique cell death modality driven by iron-dependent phospholipid peroxidation manifested as an accumulation of lipid-reactive oxygen species. With further understanding of noncoding RNAs (ncRNAs), numerous studies have demonstrated an important regulatory role of ncRNAs in ESCC through ferroptosis, including microRNAs, long ncRNAs, and circular RNAs. These ncRNAs influence the expression of the target gene to regulate ESCC progression by involving the ferroptosis signaling pathway. However, the specific regulatory mechanism of ncRNAs on ferroptosis in ESCC remains largely unknown. This review summarized the current knowledge on the relation between ferroptosis regulators, such as glutathione synthesis/metabolism, Keap1/Nfr2, and p53, by ncRNAs and ESCC. This review also proposed the possible therapeutic approaches for ncRNAs targeting ferroptosis in ESCC. This is the latest and most effective summary of recent research achievements of ncRNAs on ferroptosis in ESCC. These ncRNAs based on ferroptosis merit further investigation in preclinical research of ESCC.
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Affiliation(s)
- Guanen Qiao
- Department of Gastroenterology, The First Hospital of Handan City, 25 Congtai Road, Handan, 056002, Hebei, China.
| | - Wenjuan Zhang
- Department of Gastroenterology, The First Hospital of Handan City, 25 Congtai Road, Handan, 056002, Hebei, China
| | - Kui Dong
- Department of Gastroenterology, The First Hospital of Handan City, 25 Congtai Road, Handan, 056002, Hebei, China
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A Pleiotropic Role of Long Non-Coding RNAs in the Modulation of Wnt/β-Catenin and PI3K/Akt/mTOR Signaling Pathways in Esophageal Squamous Cell Carcinoma: Implication in Chemotherapeutic Drug Response. Curr Oncol 2022; 29:2326-2349. [PMID: 35448163 PMCID: PMC9031703 DOI: 10.3390/curroncol29040189] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 03/19/2022] [Accepted: 03/20/2022] [Indexed: 02/06/2023] Open
Abstract
Despite the availability of modern techniques for the treatment of esophageal squamous cell carcinoma (ESCC), tumor recurrence and metastasis are significant challenges in clinical management. Thus, ESCC possesses a poor prognosis and low five-year overall survival rate. Notably, the origin and recurrence of the cancer phenotype are under the control of complex cancer-related signaling pathways. In this review, we provide comprehensive knowledge about long non-coding RNAs (lncRNAs) related to Wnt/β-catenin and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway in ESCC and its implications in hindering the efficacy of chemotherapeutic drugs. We observed that a pool of lncRNAs, such as HERES, TUG1, and UCA1, associated with ESCC, directly or indirectly targets various molecules of the Wnt/β-catenin pathway and facilitates the manifestation of multiple cancer phenotypes, including proliferation, metastasis, relapse, and resistance to anticancer treatment. Additionally, several lncRNAs, such as HCP5 and PTCSC1, modulate PI3K/Akt/mTOR pathways during the ESCC pathogenesis. Furthermore, a few lncRNAs, such as AFAP1-AS1 and LINC01014, block the efficiency of chemotherapeutic drugs, including cisplatin, 5-fluorouracil, paclitaxel, and gefitinib, used for ESCC treatment. Therefore, this review may help in designing a better therapeutic strategy for ESCC patients.
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Hui B, Lu C, Wang J, Xu Y, Yang Y, Ji H, Li X, Xu L, Wang J, Tang W, Wang K, Gu Y. Engineered exosomes for co-delivery of PGM5-AS1 and oxaliplatin to reverse drug resistance in colon cancer. J Cell Physiol 2021; 237:911-933. [PMID: 34463962 DOI: 10.1002/jcp.30566] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 08/13/2021] [Accepted: 08/14/2021] [Indexed: 02/06/2023]
Abstract
Oxaliplatin resistance inevitably occurs in almost all cases of metastatic colorectal cancer (CRC), and it is important to study the roles of lncRNAs and their specific regulatory mechanisms in oxaliplatin resistance. Exosomes are increasingly designed for drug or functional nucleic acid delivery due to their properties, thereby improving the effectiveness of cancer therapy. The results of this study show that the low expression of PGM5 antisense RNA 1 (PGM5-AS1) in colon cancer is induced by transcription inhibitor, GFI1B. PGM5-AS1 prevents proliferation, migration, and acquired oxaliplatin tolerance of colon cancer cells. Exosomes encapsulating oxaliplatin and PGM5-AS1 can reverse drug resistance. For identifying differentially expressed target genes regarding PGM5-AS1, RNA transcriptome sequencing was performed. The mechanism by which PGM5-AS1 regulates its target genes was explored by performing experiments such as fluorescent in situ hybridization assay, dual-luciferase reporter gene assay, and RNA immunoprecipitation. The results show that by recruiting SRSF3, PGM5-AS1 activates alternate splicing to downregulate PAEP expression. For hsa-miR-423-5p, PGM5-AS1 can also act as a sponge to upregulate the NME1 expression.
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Affiliation(s)
- Bingqing Hui
- Department of Oncology and Cancer Rehabilitation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.,The First Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Chen Lu
- The First Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu, China.,Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Jing Wang
- State Key Laboratory of Reproductive Medicine, Department of Anatomy, Histology and Embryology, The Research Center for Bone and Stem Cells, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yetao Xu
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yuchen Yang
- Department of Oncology and Cancer Rehabilitation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.,The First Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Hao Ji
- Department of Liver Surgery and Liver Transplantation Center, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Xiaofei Li
- Department of Oncology and Cancer Rehabilitation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.,The First Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Lingyan Xu
- Department of Oncology and Cancer Rehabilitation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.,The First Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Jiawei Wang
- Department of Oncology and Cancer Rehabilitation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.,The First Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Weiwei Tang
- Key Laboratory of Living Donor Transplantation, Hepatobiliary/Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Chinese Academy of Medical Sciences, Nanjing, Jiangsu, China
| | - Keming Wang
- Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yanhong Gu
- Department of Oncology and Cancer Rehabilitation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.,The First Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu, China
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MiR-466 Inhibits the Progression of Severe Hepatocellular Carcinoma via Regulating FMNL2-Mediated Activation of NF- κB and Wnt/ β-Catenin Pathways. JOURNAL OF ONCOLOGY 2021; 2021:3554219. [PMID: 34257650 PMCID: PMC8249156 DOI: 10.1155/2021/3554219] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Revised: 06/02/2021] [Accepted: 06/17/2021] [Indexed: 12/16/2022]
Abstract
Hepatocellular carcinoma (HCC) has threatened the health of humans, and some evidence has indicated that miR-466 involves the progressions of some cancers. This study focused on the role of miR-466 in the formation and development of HCC. The expression levels of miR-466 in the tissues of patients and HCC cell lines were measured by qRT-PCR, and CCK-8, transwell assay, and flow cytometry assay were used to observe the functions of miR-466 on the HCC cells. Moreover, the miRNA databases, dual-luciferase reporter assay, and Western blot were used for the investigation of the regulation mechanism of miR-466 on HCC cells. The results showed that miR-466 was significantly downregulated in HCC tissues and cell lines, and inhibited proliferation, invasion, and high apoptosis were found in HCC cells when miR-466 was overexpressed. The results confirmed that FMNL2 was a target of miR-466, and increased FMNL2 could reverse the effects of miR-466 on the phenotype of HCC cells. Besides, it was also found that miR-466 was involved in the regulation of NF-κB and Wnt/β-catenin pathways in HCC cells via targeting FMNL2. In conclusion, the results of this study suggest that miR-466 regulates the activities of NF-κB and Wnt/β-catenin pathways to inhibit the progression of HCC cells via targeting FMNL2.
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11
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Xu QR, Tang J, Liao HY, Yu BT, He XY, Zheng YZ, Liu S. Long non-coding RNA MEG3 mediates the miR-149-3p/FOXP3 axis by reducing p53 ubiquitination to exert a suppressive effect on regulatory T cell differentiation and immune escape in esophageal cancer. J Transl Med 2021; 19:264. [PMID: 34140005 PMCID: PMC8212454 DOI: 10.1186/s12967-021-02907-1] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Accepted: 05/24/2021] [Indexed: 01/27/2023] Open
Abstract
Background Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) has been implicated in the progression of esophageal cancer (EC). However, the specific mechanism of the involvement of MEG3 in EC development in relation to the regulation of immune escape remains uncertain. Thus, the aim of the current study was to investigate the effect of MEG3 on EC via microRNA-149-3p (miR-149-3p). Methods Gain- and loss-of-function experiments were initially performed in EC cells in addition to the establishment of a 4-nitroquinoline 1-oxide-induced EC mouse model aimed at evaluating the respective roles of forkhead box P3 (FOXP3), MEG3, miR-149-3p, mouse double minute 2 homolog (MDM2) and p53 in T cell differentiation and immune escape observed in EC. Results EC tissues were found to exhibit upregulated FOXP3 and MDM2 while MEG3, p53 and miR-149-3p were all downregulated. FOXP3 was confirmed to be a target gene of miR-149-3p with our data suggesting it reduced p53 ubiquitination and degradation by means of inhibiting MDM2. P53 was enriched in the promoter of miR-149-3p to upregulate miR-149-3p. The overexpression of MEG3, p53 or miR-149-3p or silencing FOXP3 was associated with a decline in CD25+FOXP3+CD4+ T cells, IL-10+CD4+ T cells and IL-4+CD4+ T cells in spleen tissues, IL-4, and IL-10 levels as well as C-myc, N-myc and Ki-67 expression in EC mice. Conclusion Collectively, MEG3 decreased FOXP3 expression and resulted in repressed regulatory T cell differentiation and immune escape in EC mice by upregulating miR-149-3p via MDM2-mediated p53. Supplementary Information The online version contains supplementary material available at 10.1186/s12967-021-02907-1.
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Affiliation(s)
- Qi-Rong Xu
- Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People's Republic of China
| | - Jian Tang
- Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People's Republic of China
| | - Hong-Ying Liao
- Department of Thoracic Surgery, The Sixth Affiliated Hospital, Sun Yat-sen UniversityMedical University, No. 26, Erheng Road, Yuancun, Tianhe District, Guangzhou, 510655, Guangdong Province, P. R. China
| | - Ben-Tong Yu
- Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People's Republic of China
| | - Xiang-Yuan He
- Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People's Republic of China
| | - Yu-Zhen Zheng
- Department of Thoracic Surgery, The Sixth Affiliated Hospital, Sun Yat-sen UniversityMedical University, No. 26, Erheng Road, Yuancun, Tianhe District, Guangzhou, 510655, Guangdong Province, P. R. China.
| | - Sheng Liu
- Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People's Republic of China.
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12
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Jun T, Chen W, Hailing C, Ning W, Qinxue C. The novel circular RNA circ-PGAP3 retards cervical cancer growth by regulating the miR-769-5p/p53 axis. Hum Cell 2021; 34:878-888. [PMID: 33591461 DOI: 10.1007/s13577-021-00493-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 01/17/2021] [Indexed: 01/13/2023]
Abstract
Cervical cancer (CC) is still an intractable disease that seriously affects women's health. Elucidating its pathogenesis will bring new targets for clinical treatment. Circular RNA (circRNA) is an endogenous RNA that has recently been reported to be closely related to cancer progression and development. In the current study, by performing in silico analysis and qRT-PCR assay, we found a circRNA derived from PGAP3, referred as circ-PGAP3 (hsa_circ_0106800, chr17:37843549-37844086), which was significantly downregulated in CC tissues. Low circ-PGAP3 was closely linked to poor prognosis. And overexpression of circ-PGAP3 significantly reduced CC cell proliferation in vitro and tumor growth in vivo. In terms of mechanism, circ-PGAP3 was transcriptionally elevated by p53, a well-recognized tumor suppressor, and circ-PGAP3 was located in the cytoplasm where sponged miR-769-5p to increase the levels of p53 and its downstream targets. Importantly, the regulatory feedback loop of circ-PGAP3/p53 was also confirmed in vivo. Overall, our data clearly expounded the tumor-inhibiting role of circ-PGAP3 in CC, circ-PGAP3 repressed CC tumorigenesis via regulating the miR-769-5p/p53 axis. Therefore, restoration of circ-PGAP3 may be a promising therapeutic target for this thorny disease.
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Affiliation(s)
- Tian Jun
- Department of Gynecology, HuaiHe Hosipital of Henan University, Kaifeng, 475001, Henan, China
| | - Wang Chen
- Department of Gynecology, HuaiHe Hosipital of Henan University, Kaifeng, 475001, Henan, China.
| | - Cheng Hailing
- Department of Gynecology, HuaiHe Hosipital of Henan University, Kaifeng, 475001, Henan, China
| | - Wang Ning
- Department of Gynecology, HuaiHe Hosipital of Henan University, Kaifeng, 475001, Henan, China
| | - Cao Qinxue
- Department of Gynecology, HuaiHe Hosipital of Henan University, Kaifeng, 475001, Henan, China
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13
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Luan S, Yang Y, Zhou Y, Zeng X, Xiao X, Liu B, Yuan Y. The emerging role of long noncoding RNAs in esophageal carcinoma: from underlying mechanisms to clinical implications. Cell Mol Life Sci 2021; 78:3403-3422. [PMID: 33464385 PMCID: PMC11071794 DOI: 10.1007/s00018-020-03751-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 12/16/2020] [Accepted: 12/28/2020] [Indexed: 02/08/2023]
Abstract
Long noncoding RNAs (lncRNAs), a type of transcriptional product more than 200 nucleotides in length, have emerged as crucial regulators in human cancers. Accumulating data have recently indicated relationships between lncRNAs and esophageal carcinoma (EC). Of note, lncRNAs act as decoys/sponges, scaffolds, guides, and signals to regulate the expression of oncogenes or tumor suppressors at epigenetic, post-transcriptional, and protein levels, through which they exert their unique EC-driving or EC-suppressive functions. Moreover, the features of EC-related lncRNAs have been gradually exploited for developing novel diagnostic and therapeutic strategies in clinical scenarios. LncRNAs have the potential to be used as diagnostic and prognostic indicators individually or in combination with other clinical variables. Beyond these, although the time is not yet ripe, therapeutically targeting EC-related lncRNAs via gene editing, antisense oligonucleotides, RNA interference, and small molecules is likely one of the most promising therapeutic strategies for the next generation of cancer treatment. Herein, we focus on summarizing EC-driving/suppressive lncRNAs, as well as discussing their different features regarding expression profiles, modes of action, and oncological effects. Moreover, we further discuss current challenges and future developing possibilities of capitalizing on lncRNAs for EC early diagnosis and treatment.
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Affiliation(s)
- Siyuan Luan
- Department of Thoracic Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Yushang Yang
- Department of Thoracic Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Yuxin Zhou
- Department of Thoracic Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Xiaoxi Zeng
- West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xin Xiao
- Department of Thoracic Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Bo Liu
- Department of Thoracic Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China.
| | - Yong Yuan
- Department of Thoracic Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China.
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14
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Du L, Gao Y. PGM5-AS1 impairs miR-587-mediated GDF10 inhibition and abrogates progression of prostate cancer. J Transl Med 2021; 19:12. [PMID: 33407592 PMCID: PMC7789719 DOI: 10.1186/s12967-020-02572-w] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 10/13/2020] [Indexed: 11/12/2022] Open
Abstract
Background Prostate cancer (PCa) is a leading cause of cancer-related death in males. Aberrant expression of long non-coding RNAs (lncRNAs) has been implicated in various human malignancies, including PCa. This study aims to clarify the inhibitory role of human PGM5 antisense RNA 1 (PGM5-AS1) in the proliferation and apoptosis of PCa cells. Methods The regulatory network of PGM5-AS1/microRNA-587 (miR-587)/growth and differentiation factor 10 (GDF10) axis was examined by dual-luciferase reporter gene assay, RNA-binding protein immunoprecipitation, and RNA pull down assay. We manipulated the expression of PGM5-AS1, miR-587 and GDF10 by transducing expression vectors, mimic, inhibitor, or short hairpin RNA into PCa cells, thus establishing their functions in cell proliferation and apoptosis. Additionally, we measured the tumorigenicity of PCa cells xenografted in nude mice. Results PGM5-AS1 is expressed at low levels in PCa cell lines. Forced overexpression of PGM5-AS1 restricted proliferation and facilitated apoptosis of PCa cells, manifesting in suppressed xenograft tumor growth in nude mice. Notably, PGM5-AS1 competitively bound to miR-587, which directly targets GDF10. We further validated that the anti-cancer role of PGM5-AS1 in PCa cells was achieved by binding to miR-587 to promote the expression of GDF10. Conclusion PGM5-AS1 upregulates GDF10 gene expression by competitively binding to miR-587, thus inhibiting proliferation and accelerating apoptosis of PCa cells.
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Affiliation(s)
- Lei Du
- Department of Oncology, Linyi People's Hospital, No. 27, East Section of Jiefang RoadShandong, Linyi, 276000, People's Republic of China
| | - Yongli Gao
- Department of Oncology, Linyi People's Hospital, No. 27, East Section of Jiefang RoadShandong, Linyi, 276000, People's Republic of China.
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15
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Wang X, Chen T. CUL4A regulates endometrial cancer cell proliferation, invasion and migration by interacting with CSN6. Mol Med Rep 2020; 23:23. [PMID: 33179082 PMCID: PMC7673334 DOI: 10.3892/mmr.2020.11661] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 10/09/2020] [Indexed: 12/18/2022] Open
Abstract
Endometrial cancer (EC) is a common malignant gynecological tumor arising from the endometrium, with an annually increasing morbidity and mortality. The present study aimed to investigate the functions of cullin 4A (CUL4A) in EC, as well as the underlying mechanisms. CUL4A expression was assessed in several human EC cells and normal human endometrial epithelial cells (hEECs) via reverse transcription‑quantitative polymerase chain reaction and western blotting. Subsequently, short hairpin (sh)RNA‑CULA4 was transfected into cells, and cell proliferation, invasion and migration were detected using Cell Counting kit‑8, Transwell and wound healing assays, respectively. The STRING database identified that CSN6 interacted with CULA4, and immunoprecipitation was performed to verify the interaction. Subsequently, following CUL4A knockdown, pcDNA3.1‑CSN6 was transfected into cells and its effects on cell proliferation, invasion and migration were assessed. The expression levels of matrix metallopeptidase (MMP)2, MMP9 and p53 were evaluated via western blotting. The results indicated that CUL4A was highly expressed in EC cells, compared with hEECs. CULA4‑knockdown notably inhibited EC cell proliferation, invasion and migration. The expression levels of MMP2 and MMP9 were significantly decreased, while p53 expression was enhanced following CUL4A‑knockdown. The immunoprecipitation assay verified that COP9 signalosome subunit 6 (CSN6) interacted with CULA4. Furthermore, CSN6‑overexpression alleviated the inhibitory effects of CUL4A‑knockdown on EC cell proliferation, invasion and migration. Similarly, CSN6 overexpression reversed CUL4A‑knockdown‑mediated effects on the expression of MMP2, MMP9 and p53. In summary, the results demonstrated that CUL4A regulated EC cell proliferation, invasion and migration by interacting with CSN6.
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Affiliation(s)
- Xiangrong Wang
- Nursing Department, Jiangsu Union Technical Institute Nantong Health Branch, Nantong, Jiangsu 226010, P.R. China
| | - Tianquan Chen
- Department of Gynecology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225000, P.R. China
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16
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Xie Y, Zhang J, Lu B, Bao Z, Zhao J, Lu X, Wei Y, Yao K, Jiang Y, Yuan Q, Zhang X, Li B, Chen X, Dong Z, Liu K. Mefloquine Inhibits Esophageal Squamous Cell Carcinoma Tumor Growth by Inducing Mitochondrial Autophagy. Front Oncol 2020; 10:1217. [PMID: 32850358 PMCID: PMC7400730 DOI: 10.3389/fonc.2020.01217] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 06/15/2020] [Indexed: 12/12/2022] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) has a worldwide impact on human health, due to its high incidence and mortality. Therefore, identifying compounds to increase patients' survival rate is urgently needed. Mefloquine (MQ) is an FDA-approved anti-malarial drug, which has been reported to inhibit cellular proliferation in several cancers. However, the anti-tumor activities of the drug have not yet been completely defined. In this study, mass spectrometry was employed to profile proteome changes in ESCC cells after MQ treatment. Sub-cellular localization and gene ontology term enrichment analysis suggested that MQ treatment mainly affect mitochondria. The KEGG pathway enrichment map of down-regulated pathways and Venn diagram indicated that all of the top five down regulated signaling pathways contain four key mitochondrial proteins (succinate dehydrogenase complex subunit C (SDHC), succinate dehydrogenase complex subunit D, mitochondrially encoded cytochrome c oxidase III and NADH: ubiquinone oxidoreductase subunit V3). Meanwhile, mitochondrial autophagy was observed in MQ-treated KYSE150 cells. More importantly, patient-derived xenograft mouse models of ESCC with SDHC high expression were more sensitive to MQ treatment than low SDHC-expressing xenografts. Taken together, mefloquine inhibits ESCC tumor growth by inducing mitochondrial autophagy and SDHC plays a vital role in MQ-induced anti-tumor effect on ESCC.
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Affiliation(s)
- Yifei Xie
- Department of Pathophysiology, School of Basic Medical Sciences, AMS, Zhengzhou University, Zhengzhou, China
| | - Jing Zhang
- Department of Pathophysiology, School of Basic Medical Sciences, AMS, Zhengzhou University, Zhengzhou, China
| | - Bingbing Lu
- Department of Pathophysiology, School of Basic Medical Sciences, AMS, Zhengzhou University, Zhengzhou, China
| | - Zhuo Bao
- Department of Pathophysiology, School of Basic Medical Sciences, AMS, Zhengzhou University, Zhengzhou, China
| | - Jimin Zhao
- Department of Pathophysiology, School of Basic Medical Sciences, AMS, Zhengzhou University, Zhengzhou, China.,Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, China
| | - Xianyu Lu
- Department of Pathophysiology, School of Basic Medical Sciences, AMS, Zhengzhou University, Zhengzhou, China
| | - Yaxing Wei
- Department of Pathophysiology, School of Basic Medical Sciences, AMS, Zhengzhou University, Zhengzhou, China
| | - Ke Yao
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
| | - Yanan Jiang
- Department of Pathophysiology, School of Basic Medical Sciences, AMS, Zhengzhou University, Zhengzhou, China
| | - Qiang Yuan
- Department of Pathophysiology, School of Basic Medical Sciences, AMS, Zhengzhou University, Zhengzhou, China
| | - Xiaofan Zhang
- Department of Pathophysiology, School of Basic Medical Sciences, AMS, Zhengzhou University, Zhengzhou, China
| | - Bo Li
- Department of Pathophysiology, School of Basic Medical Sciences, AMS, Zhengzhou University, Zhengzhou, China
| | - Xinhuan Chen
- Department of Pathophysiology, School of Basic Medical Sciences, AMS, Zhengzhou University, Zhengzhou, China.,Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, China
| | - Zigang Dong
- Department of Pathophysiology, School of Basic Medical Sciences, AMS, Zhengzhou University, Zhengzhou, China.,China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China.,Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, China
| | - Kangdong Liu
- Department of Pathophysiology, School of Basic Medical Sciences, AMS, Zhengzhou University, Zhengzhou, China.,Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, China.,China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China.,Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, China
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17
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Chu LY, Peng YH, Weng XF, Xie JJ, Xu YW. Blood-based biomarkers for early detection of esophageal squamous cell carcinoma. World J Gastroenterol 2020; 26:1708-1725. [PMID: 32351288 PMCID: PMC7183865 DOI: 10.3748/wjg.v26.i15.1708] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2019] [Revised: 03/13/2020] [Accepted: 03/19/2020] [Indexed: 02/06/2023] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor of the digestive system worldwide, especially in China. Due to the lack of effective early detection methods, ESCC patients often present at an advanced stage at the time of diagnosis, which seriously affects the prognosis of patients. At present, early detection of ESCC mainly depends on invasive and expensive endoscopy and histopathological biopsy. Therefore, there is an unmet need for a non-invasive method to detect ESCC in the early stages. With the emergence of a large class of non-invasive diagnostic tools, serum tumor markers have attracted much attention because of their potential for detection of early tumors. Therefore, the identification of serum tumor markers for early detection of ESCC is undoubtedly one of the most effective ways to achieve early diagnosis and treatment of ESCC. This article reviews the recent advances in the discovery of blood-based ESCC biomarkers, and discusses the origins, clinical applications, and technical challenges of clinical validation of various types of biomarkers.
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Affiliation(s)
- Ling-Yu Chu
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Yu-Hui Peng
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
- Precision Medicine Research Center, Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Xue-Fen Weng
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
- Precision Medicine Research Center, Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Jian-Jun Xie
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong Province, China
- Precision Medicine Research Center, Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Yi-Wei Xu
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
- Precision Medicine Research Center, Shantou University Medical College, Shantou 515041, Guangdong Province, China
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18
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Li HM, Yu YK, Liu Q, Wei XF, Zhang J, Zhang RX, Sun HB, Wang ZF, Xing WQ, Li Y. LncRNA SNHG1 Regulates the Progression of Esophageal Squamous Cell Cancer by the miR-204/HOXC8 Axis. Onco Targets Ther 2020; 13:757-767. [PMID: 32158227 PMCID: PMC6986417 DOI: 10.2147/ott.s224550] [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] [Received: 07/24/2019] [Accepted: 12/24/2019] [Indexed: 12/14/2022] Open
Abstract
Objective Long noncoding RNA small nucleolar RNA host gene 1 (SNHG1) has been reported to be aberrantly expressed and plays an important role in human cancers, including esophageal squamous cell cancer. However, the regulatory mechanism underlying SNHG1 in the progression of esophageal squamous cell cancer is poorly defined. Materials and Methods Fifty-three esophageal squamous cell cancer patients were recruited and overall survival was analyzed. EC9706 and KYSE150 cells were cultured for study in vitro. The expression levels of SNHG1, microRNA (miR)-204 and homeobox c8 (HOXC8) were detected by quantitative real-time polymerase chain reaction and Western blot. Cell cycle distribution, apoptosis, migration and invasion were determined by flow cytometry and transwell assays, respectively. The target interaction among SNHG1, miR-204 and HOXC8 was validated by luciferase reporter assay and RNA immunoprecipitation. Xenograft model was established to investigate the role of SNHG1 in vivo. Results High expression of SNHG1 was exhibited in esophageal squamous cell cancer and indicated poor outcomes of patients. SNHG1 silence led to cell cycle arrest at G0-G1 phase, inhibition of migration and invasion and increase of apoptosis. miR-204 was validated to sponge by SNHG1 and target HOXC8 in esophageal squamous cell cancer cells. miR-204 knockdown or HOXC8 restoration reversed the inhibitive role of SNHG1 silence in the progression of esophageal squamous cell cancer cells. Furthermore, inhibiting SNHG1 decreased xenograft tumor growth by regulating miR-204 and HOXC8. Conclusion SNHG1 knockdown suppresses migration and invasion but induces apoptosis of esophageal squamous cell cancer cells by increasing miR-204 and decreasing HOXC8.
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Affiliation(s)
- Hao Miao Li
- Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Yong Kui Yu
- Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Qi Liu
- Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Xiu Feng Wei
- Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Jun Zhang
- Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Rui Xiang Zhang
- Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Hai Bo Sun
- Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Zong Fei Wang
- Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Wen Qun Xing
- Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Yin Li
- Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China.,Department of Thoracic Surgery, The Cancer Hospital Chinese Academy of Medical Sciences, Beijing, People's Republic of China
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19
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Lin X, Kapoor A, Gu Y, Chow MJ, Xu H, Major P, Tang D. Assessment of biochemical recurrence of prostate cancer (Review). Int J Oncol 2019; 55:1194-1212. [PMID: 31638194 PMCID: PMC6831208 DOI: 10.3892/ijo.2019.4893] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Accepted: 09/24/2019] [Indexed: 12/12/2022] Open
Abstract
The assessment of the risk of biochemical recurrence (BCR) is critical in the management of males with prostate cancer (PC). Over the past decades, a comprehensive effort has been focusing on improving risk stratification; a variety of models have been constructed using PC-associated pathological features and molecular alterations occurring at the genome, protein and RNA level. Alterations in RNA expression (lncRNA, miRNA and mRNA) constitute the largest proportion of the biomarkers of BCR. In this article, we systemically review RNA-based BCR biomarkers reported in PubMed according to the PRISMA guidelines. Individual miRNAs, mRNAs, lncRNAs and multi-gene panels, including the commercially available signatures, Oncotype DX and Prolaris, will be discussed; details related to cohort size, hazard ratio and 95% confidence intervals will be provided. Mechanistically, these individual biomarkers affect multiple pathways critical to tumorigenesis and progression, including epithelial-mesenchymal transition (EMT), phosphatase and tensin homolog (PTEN), Wnt, growth factor receptor, cell proliferation, immune checkpoints and others. This variety in the mechanisms involved not only validates their associations with BCR, but also highlights the need for the coverage of multiple pathways in order to effectively stratify the risk of BCR. Updates of novel biomarkers and their mechanistic insights are considered, which suggests new avenues to pursue in the prediction of BCR. Additionally, the management of patients with BCR and the potential utility of the stratification of the risk of BCR in salvage treatment decision making for these patients are briefly covered. Limitations will also be discussed.
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Affiliation(s)
- Xiaozeng Lin
- Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada
| | - Anil Kapoor
- The Research Institute of St. Joe's Hamilton, St. Joseph's Hospital, Hamilton, ON L8N 4A6, Canada
| | - Yan Gu
- Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada
| | - Mathilda Jing Chow
- Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada
| | - Hui Xu
- Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
| | - Pierre Major
- Division of Medical Oncology, Department of Oncology, McMaster University, Hamilton, ON L8V 5C2, Canada
| | - Damu Tang
- Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada
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