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Pordel S, Khorrami M, Saadatpour F, Rezaee D, Cho WC, Jahani S, Aghaei-Zarch SM, Hashemi E, Najafi S. The role of microRNA-185 in the pathogenesis of human diseases: A focus on cancer. Pathol Res Pract 2023; 249:154729. [PMID: 37639952 DOI: 10.1016/j.prp.2023.154729] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 07/29/2023] [Indexed: 08/31/2023]
Abstract
MicroRNAs (miRNAs) are a widely-studied class of non-coding RNAs characterized by their short length (18-25 nucleotides). The precise functions of miRNAs are not well-elucidated; however, an increasing number of studies suggest their involvement in various physiologic processes and deregulation in pathologic conditions. miRNA-185 (miR-185) is among the mostly-studied miRNAs in human diseases, which is found to play putative roles in conditions like metabolic disorders, asthma, frailty, schizophrenia, and hepatitis. Notably, many cancer studies report the downregulation of miR-185 in cell lines, tumor tissues, and plasma specimens of patients, while it demonstrates a suppressing role on the malignant properties of cancer cells in vitro and in vivo. Accordingly, miR-185 can be considered a tumor suppressor miRNA in human malignancies, while a few studies also report inconsistent findings. Being suggested as a prognostic/diagnostic biomarker, mi-185 is also found to offer clinical potentials, particularly for early diagnosis and prediction of the prognosis of cancer patients. In this review, we have outlined the studies that have evaluated the functions and clinical significance of miR-185 in different human diseases with a particular focus on cancer.
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Affiliation(s)
- Safoora Pordel
- Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Immunology and Allergy, The Persian Gulf Tropical Medicine Research Center, The Persian Gulf Biomedical Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Motahare Khorrami
- Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Fatemeh Saadatpour
- Pharmaceutical Biotechnology Lab, Department of Microbiology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran
| | - Delsuz Rezaee
- School of Allied Medical Sciences, Ilam University of Medical Sciences, Ilam, Iran
| | - William C Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, 30 Gascoigne Road, Hong Kong, China
| | | | - Seyed Mohsen Aghaei-Zarch
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Elham Hashemi
- Department of Anatomical Sciences, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Sajad Najafi
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Bhattacharjee R, Prabhakar N, Kumar L, Bhattacharjee A, Kar S, Malik S, Kumar D, Ruokolainen J, Negi A, Jha NK, Kesari KK. Crosstalk between long noncoding RNA and microRNA in Cancer. Cell Oncol (Dordr) 2023; 46:885-908. [PMID: 37245177 PMCID: PMC10356678 DOI: 10.1007/s13402-023-00806-9] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/26/2023] [Indexed: 05/29/2023] Open
Abstract
miRNAs and lncRNAs play a central role in cancer-associated gene regulations. The dysregulated expression of lncRNAs has been reported as a hallmark of cancer progression, acting as an independent prediction marker for an individual cancer patient. The interplay of miRNA and lncRNA decides the variation of tumorigenesis that could be mediated by acting as sponges for endogenous RNAs, regulating miRNA decay, mediating intra-chromosomal interactions, and modulating epigenetic components. This paper focuses on the influence of crosstalk between lncRNA and miRNA on cancer hallmarks such as epithelial-mesenchymal transition, hijacking cell death, metastasis, and invasion. Other cellular roles of crosstalks, such as neovascularization, vascular mimicry, and angiogenesis were also discussed. Additionally, we reviewed crosstalk mechanism with specific host immune responses and targeting interplay (between lncRNA and miRNA) in cancer diagnosis and management.
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Affiliation(s)
- Rahul Bhattacharjee
- KIIT School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT-DU), Bhubaneswar, Odisha, India
| | - Neeraj Prabhakar
- Centre for Structural System Biology, Department of Physics, University of Hamburg, c/o DESY, Building 15, Notkestr. 852267, Hamburg, Germany
- Pharmacy, Abo Akademi University, Tykistökatu 6A, Turku, Finland
| | - Lamha Kumar
- School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram, India
| | - Arkadyuti Bhattacharjee
- KIIT School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT-DU), Bhubaneswar, Odisha, India
| | - Sulagna Kar
- KIIT School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT-DU), Bhubaneswar, Odisha, India
| | - Sumira Malik
- Amity Institute of Biotechnology, Amity University Jharkhand, Ranchi, Jharkhand, 834001, India
| | - Dhruv Kumar
- School of Health Sciences and Technology (SoHST), UPES University, Dehradun, Uttarakhand, India
| | - Janne Ruokolainen
- Department of Applied Physics, School of Science, Aalto University, Espoo, 00076, Finland
| | - Arvind Negi
- Department of Bioproducts and Biosystems, School of Chemical Engineering, Aalto University, Espoo, 00076, Finland.
| | - Niraj Kumar Jha
- Department of Biotechnology, School of Engineering and Technology (SET), Sharda University, Greater Noida, 201310, UP, India.
- School of Bioengineering & Biosciences, Lovely Professional University, Phagwara, 144411, India.
- Department of Biotechnology, School of Applied & Life Sciences (SALS), Uttaranchal University, Dehradun, 248007, India.
| | - Kavindra Kumar Kesari
- Department of Applied Physics, School of Science, Aalto University, Espoo, 00076, Finland.
- Faculty of Biological and Environmental Sciences, University of Helsinki, Biocentre 3, Helsinki, Finland.
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Dashti F, Mirazimi SMA, Kazemioula G, Mohammadi M, Hosseini M, Razaghi Bahabadi Z, Mirazimi MS, Abadi MHJN, Shahini A, Afshari M, Mirzaei H. Long non-coding RNAs and melanoma: From diagnosis to therapy. Pathol Res Pract 2023; 241:154232. [PMID: 36528985 DOI: 10.1016/j.prp.2022.154232] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Revised: 11/16/2022] [Accepted: 11/16/2022] [Indexed: 11/29/2022]
Abstract
Although extremely rare, malignant melanoma is the deadliest type of skin malignancy with the inherent capability to invade other organs and metastasize to distant tissues. In 2021, it was estimated that approximately 106,110 patients may have received the diagnosis of melanoma, with a mortality rate of 7180. Surgery remains the common choice for treatment in patients with melanoma. Despite many advances in the treatment of melanoma, some patients, such as those who have received cytotoxic chemotherapeutic and immunotherapic agents, a significant number of patients may show inadequate treatment response following initiating these treatments. Non-coding RNAs, including lncRNAs, have become recently popular and attracted the attention of many researchers to make new insights into the pathogenesis of many diseases, particularly malignancies. LncRNAs have been thoroughly investigated in multiple cancers such as melanoma and have been shown to play a major role in regulating various physiological and pathological cellular processes. Considering their core regulatory function, these non-coding RNAs may be appropriate candidates for melanoma patients' diagnosis, prognosis, and treatment. In this review, we will cover all the current literature available for lncRNAs in melanoma and will discuss their potential benefits as diagnostic and/or prognostic markers or potent therapeutic targets in the treatment of melanoma patients.
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Affiliation(s)
- Fatemeh Dashti
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Seyed Mohammad Ali Mirazimi
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Golnesa Kazemioula
- Department of Medical Genetics, School of Medicine,Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Mohammadi
- Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Marjan Hosseini
- Department of Physiology-Pharmacology-Medical Physic, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
| | - Zahra Razaghi Bahabadi
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Maryam Sadat Mirazimi
- Department of Obstetrics & Gynocology,Isfahan School of Medicine,Isfahan University of Medical Sciences, Isfahan, Iran
| | | | - Ali Shahini
- Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Maryam Afshari
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
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Qiu Y, Wang HT, Zheng XF, Huang X, Meng JZ, Huang JP, Wen ZP, Yao J. Autophagy-related long non-coding RNA prognostic model predicts prognosis and survival of melanoma patients. World J Clin Cases 2022; 10:3334-3351. [PMID: 35611195 PMCID: PMC9048552 DOI: 10.12998/wjcc.v10.i11.3334] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 10/29/2021] [Accepted: 01/17/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Melanomas are malignant tumors that can occur in different body parts or tissues such as the skin, mucous membrane, uvea, and pia mater. Long non-coding RNAs (lncRNAs) are key factors in the occurrence and development of many malignant tumors, and are involved in the prognosis of some patients.
AIM To identify autophagy-related lncRNAs in melanoma that are crucial for the diagnosis, treatment, and prognosis of melanoma patients.
METHODS We retrieved transcriptome expression profiles and clinical information of 470 melanoma patients from The Cancer Genome Atlas (TCGA) database. Then, we identified autophagy-related genes in the Human Autophagy Database. Using R, coexpression analysis of lncRNAs and autophagy-related genes was conducted to obtain autophagy-related lncRNAs and their expression levels. We also performed univariate and multivariate Cox proportional risk analyses on the obtained datasets, to systematically evaluate the prognostic value of autophagy-related lncRNAs in melanoma. Fifteen autophagy-related lncRNAs were identified and an autophagy-related prognostic signature for melanoma was established. The Kaplan-Meier and univariate and multivariate Cox regression analyses were used to calculate risk scores. Based on the risk scores, melanoma patients were randomly divided into high- and low-risk groups. Receiver operating characteristic curve analysis, dependent on time, was performed to assess the accuracy of the prognostic model. At the same time, we also downloaded the melanoma data sets GSE65904, GSE19234, and GSE78220 from the GENE EXPRESSION OMNIBUS database for model verification. Finally, we performed Gene Set Enrichment Analysis functional annotation, which showed that the low and the high-risk groups had different enriched pathways.
RESULTS The co-expression network for autophagy-related genes was constructed using R, and 936 lncRNAs related to autophagy were identified. Then, 52 autophagy-related lncRNAs were significantly associated with TCGA melanoma patients’ survival by univariate Cox proportional risk analysis (P < 0.01). Further, the 52 autophagy-related lncRNAs mentioned above were analyzed by multivariate Cox analysis with R. Fifteen lncRNAs were selected: LINC01943, AC090948.3, USP30-AS1, AC068282.1, AC004687.1, AL133371.2, AC242842.1, PCED1B-AS1, HLA-DQB1-AS1, AC011374.2, LINC00324, AC018553.1, LINC00520, DBH-AS1, and ITGB2-AS1. The P values in all survival analyses using these 15 lncRNAs were < 0.05. These lncRNAs were used to build a risk model based on the risk score. Negative correlations were observed between risk scores and overall survival rate in melanoma patients over time. Additionally, the melanoma risk curve and scatter plot analyses showed that the death number increased along with the increase in the risk score. Overall, we identified and established a new prognostic risk model for melanoma using 15 autophagy-related lncRNAs. The risk model constructed with these lncRNAs can help and guide melanoma patient prognosis predictions and individualized treatments in the future.
CONCLUSION Overall, the risk model developed based on the 15 autophagy-related lncRNAs can have important prognostic value and may provide autophagy-related clinical targets for melanoma treatment.
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Affiliation(s)
- Yue Qiu
- Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
- Department of Bone and Joint Surgery, Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
| | - Hong-Tao Wang
- Department of Orthopedics, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
| | - Xi-Fan Zheng
- Department of Bone and Joint Surgery, Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
| | - Xing Huang
- Department of Bone and Joint Surgery, Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
| | - Jin-Zhi Meng
- Department of Bone and Joint Surgery, Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
| | - Jun-Pu Huang
- Department of Bone and Joint Surgery, Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
| | - Zhen-Pei Wen
- Department of Bone and Joint Surgery, Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
| | - Jun Yao
- Department of Orthopedics, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
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Yang G, Tian Y, Li C, Xia J, Qi Y, Yao W, Hao C. LncRNA UCA1 regulates silicosis-related lung epithelial cell-to-mesenchymal transition through competitive adsorption of miR-204-5p. Toxicol Appl Pharmacol 2022; 441:115977. [DOI: 10.1016/j.taap.2022.115977] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Revised: 03/04/2022] [Accepted: 03/08/2022] [Indexed: 11/30/2022]
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Montico B, Giurato G, Pecoraro G, Salvati A, Covre A, Colizzi F, Steffan A, Weisz A, Maio M, Sigalotti L, Fratta E. The pleiotropic roles of circular and long noncoding RNAs in cutaneous melanoma. Mol Oncol 2022; 16:565-593. [PMID: 34080276 PMCID: PMC8807361 DOI: 10.1002/1878-0261.13034] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 04/30/2021] [Accepted: 05/17/2021] [Indexed: 12/14/2022] Open
Abstract
Cutaneous melanoma (CM) is a very aggressive disease, often characterized by unresponsiveness to conventional therapies and high mortality rates worldwide. The identification of the activating BRAFV600 mutations in approximately 50% of CM patients has recently fueled the development of novel small-molecule inhibitors that specifically target BRAFV600 -mutant CM. In addition, a major progress in CM treatment has been made by monoclonal antibodies that regulate the immune checkpoint inhibitors. However, although target-based therapies and immunotherapeutic strategies have yielded promising results, CM treatment remains a major challenge. In the last decade, accumulating evidence points to the aberrant expression of different types of noncoding RNAs (ncRNAs) in CM. While studies on microRNAs have grown exponentially leading to significant insights on CM biology, the role of circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs) in this tumor is less understood, and much remains to be discovered. Here, we summarize and critically review the available evidence on the molecular functions of circRNAs and lncRNAs in BRAFV600 -mutant CM and CM immunogenicity, providing recent updates on their functional role in targeted therapy and immunotherapy resistance. In addition, we also include an evaluation of several algorithms and databases for prediction and validation of circRNA and lncRNA functional interactions.
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Affiliation(s)
- Barbara Montico
- Immunopathology and Cancer BiomarkersCentro di Riferimento Oncologico di Aviano (CRO)IRCCSAvianoItaly
| | - Giorgio Giurato
- Laboratory of Molecular Medicine and GenomicsDepartment of Medicine, Surgery and Dentistry 'Scuola Medica Salernitana'University of SalernoBaronissiItaly
- Genome Research Center for Health – CRGSUniversity of Salerno Campus of MedicineBaronissiItaly
| | - Giovanni Pecoraro
- Laboratory of Molecular Medicine and GenomicsDepartment of Medicine, Surgery and Dentistry 'Scuola Medica Salernitana'University of SalernoBaronissiItaly
- Genome Research Center for Health – CRGSUniversity of Salerno Campus of MedicineBaronissiItaly
| | - Annamaria Salvati
- Laboratory of Molecular Medicine and GenomicsDepartment of Medicine, Surgery and Dentistry 'Scuola Medica Salernitana'University of SalernoBaronissiItaly
| | - Alessia Covre
- Center for Immuno‐OncologyUniversity Hospital of SienaItaly
- University of SienaItaly
| | - Francesca Colizzi
- Immunopathology and Cancer BiomarkersCentro di Riferimento Oncologico di Aviano (CRO)IRCCSAvianoItaly
| | - Agostino Steffan
- Immunopathology and Cancer BiomarkersCentro di Riferimento Oncologico di Aviano (CRO)IRCCSAvianoItaly
| | - Alessandro Weisz
- Laboratory of Molecular Medicine and GenomicsDepartment of Medicine, Surgery and Dentistry 'Scuola Medica Salernitana'University of SalernoBaronissiItaly
- Genome Research Center for Health – CRGSUniversity of Salerno Campus of MedicineBaronissiItaly
| | - Michele Maio
- Center for Immuno‐OncologyUniversity Hospital of SienaItaly
- University of SienaItaly
- NIBIT Foundation OnlusSienaItaly
| | - Luca Sigalotti
- Oncogenetics and Functional Oncogenomics UnitCentro di Riferimento Oncologico di Aviano (CRO)IRCCSAvianoItaly
| | - Elisabetta Fratta
- Immunopathology and Cancer BiomarkersCentro di Riferimento Oncologico di Aviano (CRO)IRCCSAvianoItaly
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Wang Y, Zhang J, Liu M, Zhang S, Wang W, Cheng S. Clinical values and potential pathways of miR-183-5p in gastric cancer: a study based on integrational bioinformatics analysis. J Gastrointest Oncol 2021; 12:2123-2131. [PMID: 34790379 DOI: 10.21037/jgo-21-599] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 10/20/2021] [Indexed: 12/24/2022] Open
Abstract
Background The clinicopathological value and exploration of the potential molecular mechanism of microRNA-183-5p (miR-183-5p) have been investigated in various cancers. This study further explored the transcriptome profile regulated by miR-183-5p. Methods Messenger RNA (mRNA) expression data, miRNA expression, and clinical information of stomach adenocarcinoma (STAD) were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) that related to mir-189-5p expression and cancer proliferation were acquired using bioinformatics analysis. The biological functions of these genes were analyzed in terms of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Hub genes relating to gastric cancer (GC) signal pathway were explored. The results were validated by further experiments. Results A total of 308 genes were found to be regulated by miR-183-5p, and they were related to cancer and GC patients' survival outcome. The biological function of these genes was found to act mainly on biological processes and the involved signal pathways included neuroactive ligand-receptor interaction, cell adhesion molecules, and axon guidance. In addition, miR-183-5p was also shown to regulate the mTOR, Wnt, MAPK, and PI3K-Akt signaling pathways through the genes WNT2B, NGFR, and NTRK2. Conclusions The miRNA miR-183-5p participates in the tumorigenesis and development of GC via certain signaling pathways, in particular the nerve- and immunity-related genes.
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Affiliation(s)
- Yanan Wang
- Department of Pathology, Affiliated Hospital of Hebei University, Baoding, China
| | - Jinku Zhang
- Department of Pathology, No. 1 Central Hospital of Baoding, Baoding, China
| | - Mingkai Liu
- Department of Pathology, Affiliated Hospital of Hebei University, Baoding, China
| | - Shun Zhang
- Department of Pathology, Affiliated Hospital of Hebei University, Baoding, China
| | - Weina Wang
- Department of Pathology, Affiliated Hospital of Hebei University, Baoding, China
| | - Shujie Cheng
- Department of Surgery, Affiliated Hospital of Hebei University, Baoding, China
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HES5 Activates Long Noncoding RNA UCA1 to Induce Colorectal Cancer Progression by Modulating miR-185/NOTCH3 Signaling. Gastroenterol Res Pract 2021; 2021:7249818. [PMID: 34733326 PMCID: PMC8560272 DOI: 10.1155/2021/7249818] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Revised: 10/05/2021] [Accepted: 10/07/2021] [Indexed: 01/01/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common diagnosed cancers around the world. The poor prognosis and high fatality caused by metastasis are still the challenges for clinical treatment. Therefore, it is promising to clarify the detailed molecular mechanism of CRC metastasis. Accumulating evidences indicate that long noncoding RNAs (lncRNAs) play important roles in cancer progression including CRC. In this study, the function of lncRNA UCA1 was investigated. UCA1 was confirmed to be highly expressed in colorectal cancer. Moreover, the UCA1 expression level was positively related to tumor stages. Silencing UCA1 showed inhibitory effect on cell proliferation and metastasis. Both UCA1 and NOTCH3 were validated as direct targets of miR-185. Silencing UCA1 repressed NOTCH3 expression through the miR-185 sponge. NOTCH3 was found to be highly expressed in CRC patients and positively related to UCA1 expression. Furthermore, HES5 was verified as a transcription factor of UCA1, which induced UCA1 expression. In conclusion, UCA1 is a direct target of HES5. UCA1 promotes CRC metastasis through regulating the miR-185/NOTCH3 axis.
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Xiao Y, Xia Y, Wang Y, Xue C. Pathogenic roles of long noncoding RNAs in melanoma: Implications in diagnosis and therapies. Genes Dis 2021; 10:113-125. [PMID: 37013035 PMCID: PMC10066279 DOI: 10.1016/j.gendis.2021.08.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 07/30/2021] [Accepted: 08/20/2021] [Indexed: 12/12/2022] Open
Abstract
Melanoma is one of the most dangerous types of cutaneous neoplasms, which are pigment-producing cells of neuroectodermal origin found all over the body. A great deal of research is focused on the mechanisms of melanoma to promote better diagnostic and treatment options for melanoma in its advanced stages. The progression of melanoma involves alteration in different levels of gene expression. With the successful implementation of next-generation sequencing technology, an increasing number of long noncoding RNAs (lncRNAs) sequences have been discovered, and a significant number of them have phenotypic effects in both in vitro and in vivo studies, implying that they play an important role in the occurrence and progression of human cancers, particularly melanoma. A number of evidence indicated that lncRNAs are important regulators in tumor cell proliferation, invasion, apoptosis, immune escape, energy metabolism, drug resistance, epigenetic regulation. To better understand the role of lncRNAs in melanoma tumorigenesis, we categorize melanoma-associated lncRNAs according to their cellular functions and associations with gene expression and signaling pathways in this review. Based on the mechanisms of lncRNA, we discuss the possibility of lncRNA-target treatments, and the application of liquid biopsies to detect lncRNAs in melanoma diagnosis and prognosis.
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10
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Liu Z, Wang Y, Yuan S, Wen F, Liu J, Zou L, Zhang J. Regulatory role of long non-coding RNA UCA1 in signaling pathways and its clinical applications. Oncol Lett 2021; 21:404. [PMID: 33777227 PMCID: PMC7988699 DOI: 10.3892/ol.2021.12665] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Accepted: 02/11/2021] [Indexed: 12/15/2022] Open
Abstract
Long non-coding RNA metastasis-associated urothelial carcinoma associated 1 (UCA1) plays a pivotal role in various human diseases. Its gene expression is regulated by several factors, including transcription factors, chromatin remodeling and epigenetic modification. UCA1 is involved in the regulation of the PI3K/AKT, Wnt/β-catenin, MAPK, NF-κB and JAK/STAT signaling pathways, affecting a series of cellular biological functions, such as cell proliferation, apoptosis, migration, invasion and tumor drug resistance. Furthermore, UCA1 is used as a novel potential biomarker for disease diagnosis and prognosis, as well as a target for clinical gene therapy. The present review systematically summarizes and elucidates the mechanisms of upstream transcriptional regulation of UCA1, the regulatory role of UCA1 in multiple signaling pathways in the occurrence and development of several diseases, and its potential applications in clinical treatment.
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Affiliation(s)
- Zhaoping Liu
- Department of Rheumatology, The First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China
| | - Yanyan Wang
- Department of Rheumatology, The First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China
| | - Shunling Yuan
- Department of Rheumatology, The First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China
| | - Feng Wen
- Department of Hematology, The First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China
| | - Jing Liu
- Molecular Biology Research Center and Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410078, P.R. China
| | - Liheng Zou
- Department of Rheumatology, The First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China
| | - Ji Zhang
- Department of Rheumatology, The First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.,Department of Clinical Laboratory, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong 518033, P.R. China
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11
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Wang Y, Ba HJ, Wen XZ, Zhou M, Küçük C, Tamagnone L, Wei L, You H. A prognostic model for melanoma patients on the basis of immune-related lncRNAs. Aging (Albany NY) 2021; 13:6554-6564. [PMID: 33675585 PMCID: PMC7993708 DOI: 10.18632/aging.202730] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Accepted: 02/12/2021] [Indexed: 12/13/2022]
Abstract
The prognosis of melanoma patients is highly variable due to multiple factors conditioning immune response and driving metastatic progression. In this study, we have correlated the expression of immune-related lncRNAs with patient survival, developed a prognostic model, and investigated the characteristics of immune response in the diverse groups. The gene expression profiles and prognostic information of 470 melanoma patients were downloaded from TCGA database. Significantly predictive lncRNAs were identified by multivariate Cox regression analyses, and a prognostic model based on these variables was constructed to predict survival. Kaplan-Meier curves were plotted to estimate overall survival. The predictive accuracy of the model was evaluated by the area under the ROC curve (AUC). Principal component analysis was used to observe the distribution of immune-related genes. CIBERSORT and ESTIMATE were used to evaluate the composition of immune cells and the immune microenvironment. Eight immune-related lncRNAs were determined to be prognostic by multivariate COX regression analysis. The patient scores were calculated and divided into high- and low-risk groups. The model could effectively predict the prognosis in patients of different stages. The AUC of the model is 0.784, which was significantly higher than that of the other variables. There were significant differences in the distribution of immune-related genes between two groups; the immune score and immune function enrichment score were higher in the low risk group.
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Affiliation(s)
- Yao Wang
- Medical Oncology Department, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510095, Guangdong, China
| | - Hong-Jun Ba
- Pediatric Cardiology Department, Heart Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong, China
| | - Xi-Zhi Wen
- Biotherapy Center, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, Guangdong, China
| | - Min Zhou
- Medical Oncology Department, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510095, Guangdong, China
| | - Can Küçük
- İzmir Biomedicine and Genome Center (IBG), İzmir 35340, Turkey.,İzmir International Biomedicine and Genome Institute (iBG-İzmir), Dokuz Eylül University, İzmir 35340, Turkey.,Department of Medical Biology, Faculty of Medicine, Dokuz Eylül University, İzmir 35340, Turkey
| | - Luca Tamagnone
- Department Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Rome 00168, Italy.,Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome 00168, Italy
| | - Li Wei
- Medical Oncology Department, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510095, Guangdong, China
| | - Hua You
- Medical Oncology Department, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510095, Guangdong, China
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12
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Hosseini NF, Manoochehri H, Khoei SG, Sheykhhasan M. The Functional Role of Long Non-coding RNA UCA1 in Human Multiple Cancers: a Review Study. Curr Mol Med 2021; 21:96-110. [PMID: 32560605 DOI: 10.2174/1566524020666200619124543] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Revised: 04/30/2020] [Accepted: 05/04/2020] [Indexed: 02/08/2023]
Abstract
In various cancers, high-grade tumor and poor survival rate in patients with upregulated lncRNAs UCA1 have been confirmed. Urothelial carcinoma associated 1 (UCA1) is an oncogenic non-coding RNA with a length of more than 200 nucleotides. The UCA1 regulate critical biological processes that are involved in cancer progression, including cancer cell growth, invasion, migration, metastasis, and angiogenesis. So It should not surprise that UCA1 overexpresses in variety of cancers type, including pancreatic cancer, ovarian cancer, gastric cancer, colorectal cancer, breast cancer, prostate cancer, endometrial cancer, cervical cancer, bladder cancer, adrenal cancer, hypopharyngeal cancer, oral cancer, gallbladder cancer, nasopharyngeal cancer, laryngeal cancer, osteosarcoma, esophageal squamous cell carcinoma, renal cell carcinoma, cholangiocarcinoma, leukemia, glioma, thyroid cancer, medulloblastoma, hepatocellular carcinoma and multiple myeloma. In this article, we review the biological function and regulatory mechanism of UCA1 in several cancers and also, we will discuss the potential of its as cancer biomarker and cancer treatment.
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Affiliation(s)
- Nashmin Fayazi Hosseini
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Hamed Manoochehri
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | | | - Mohsen Sheykhhasan
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
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13
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Cao Y, Zhang R, Luo X, Yang Y. LncRNA PART1 promotes lung squamous cell carcinoma progression via miR-185-5p/Six1 axis. Hum Exp Toxicol 2020; 40:960-976. [PMID: 33300377 DOI: 10.1177/0960327120979032] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Dysregulation of the long non-coding RNA prostate androgen regulated transcript 1 (lncRNA PART1) is involved in the tumorigenesis of various cancers. However, little is known about its function and molecular mechanism in the development of lung squamous cell carcinoma (LSCC). In this study, we examined the expression of PART1 in LSCC clinical tissue samples and cell lines, and gain- and loss-of-function experiments were performed to explore the function of PART1 in LSCC proliferation, invasion and migration. We found that PART1 was overexpressed in both LSCC tissues and cell lines. Functional studies revealed that PART1 knockdown significantly suppressed cell proliferation, invasion and migration but enhanced apoptosis in LSCC cells, whereas overexpression of PART1 showed the opposite results. Mechanistically, we identified that PART1 acted as a sponge of miR-185-5p, and sineoculis homeobox homolog 1 (Six1) was a direct downstream target of miR-185-5p. Moreover, restoration of miR-185-5p or silencing of Six1 partially abolished the oncogenic effect of PART1 in LSCC cells. Clinically, The areas under the receiver operating characteristic (ROC) curve of PART1, miR-185-5p, and Six1 were 0.7857, 0.7332, 0.8112, respectively. Notably, high PART1, low miR-185-5p, and high Six1 expressions were significantly associated with severe clinical parameters and were the independent risk factors for poor prognosis of LSCC patients. Thus, we concluded that the PART1/miR-185-5p/Six1 axis might serve as a novel biomarker for the diagnosis and treatment of LSCC.
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Affiliation(s)
- Y Cao
- Department of Thoracic Surgery, 159431Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China
| | - R Zhang
- Department of Thoracic Surgery, 159431Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China
| | - X Luo
- Department of Thoracic Surgery, 159431Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China
| | - Y Yang
- Department of Thoracic Surgery, 159431Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China
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14
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Safa A, Gholipour M, Dinger ME, Taheri M, Ghafouri-Fard S. The critical roles of lncRNAs in the pathogenesis of melanoma. Exp Mol Pathol 2020; 117:104558. [PMID: 33096077 DOI: 10.1016/j.yexmp.2020.104558] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 10/12/2020] [Accepted: 10/17/2020] [Indexed: 12/14/2022]
Abstract
Long non-coding RNAs (lncRNAs) embrace a huge fraction of human transcripts and participate in the pathogenesis of human disorders especially malignant conditions. Malignant melanoma, as the most fatal type of cutaneous malignnacies, is associated with dysregulation of several lncRNAs including PVT1, H19, MALAT1, and CCAT1. Moreover, a portion of lncRNAs are exclusively expressed in melanoma cell lines. Expression levels of several lncRNAs are associated with TNM stage, tumor size and progression of melanoma. Thus, these lncRNAs are regarded as biomarkers for this malignancy. Peripheral transcript levels of a number of lncRNAs, such as PVT1, SNHG5 and SPRY4-IT1, could distinguish melanoma patients from unaffected persons with appropriate sensitivity and specificity values. Moreover, expression levels of numerous lncRNAs in tissue biopsies could differentiate malignant samples from benign samples. Based on the results of both cell line and in vivo studies, lncRNAs regulate critical pathways in the carcinogenesis of melanoma, such as the PI3K/Akt and NF-κB signaling pathways, and are involved in the modulation of response to chemotherapeutic agents. Here we review the existing information on the role of lncRNAs in malignant melanoma.
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Affiliation(s)
- Amin Safa
- Institute of Research and Development, Duy Tan University, Da Nang 550000, Viet Nam
| | - Mahdi Gholipour
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Marcel E Dinger
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, 2052 Sydney, NSW, Australia
| | - Mohammad Taheri
- Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Soudeh Ghafouri-Fard
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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15
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Hu M, Yang J. Down-regulation of lncRNA UCA1 enhances radiosensitivity in prostate cancer by suppressing EIF4G1 expression via sponging miR-331-3p. Cancer Cell Int 2020; 20:449. [PMID: 32943997 PMCID: PMC7488500 DOI: 10.1186/s12935-020-01538-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 09/03/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND We aimed to explore the role of long noncoding RNA urothelial carcinoma-associated 1 (lncRNA UCA1) and its underlying mechanism in the radioresistance of prostate cancer (PCa). METHODS QRT-PCR was conducted to measure the expression of UCA1, microRNA-331-3p (miR-331-3p) and eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) in PCa tissues and cells. The relative protein level was determined by western blot assay. Cell proliferation and apoptosis were detected by MTT, colony formation assay, and flow cytometry, respectively. The target interaction between miR-331-3p and UCA1 or EIF4G1 was predicted through bioinformatics analysis, and verified by dual-luciferase reporter gene assay system. RESULTS The high levels of UCA1 and EIF4G1 as well as the low level of miR-331-3p were observed in PCa tissues and cell lines. UCA1 and EIF4G1 expression were significantly upregulated by Gy radiation treatement. UCA1 or EIF4G1 knockdown repressed cell growth and enhanced cell apoptosis in 22RV1 and DU145 cells under radiation. Moreover, overexpression of EIF4G1 abolished UCA1 knockdown-induced effect on 6 Gy irradiated PCa cells. UCA1 sponged miR-331-3p to regulate EIF4G1 expression. CONCLUSIONS LncRNA UCA1 deletion suppressed the radioresistance to PCa by suppressing EIF4G1 expression via miR-331-3p. UCA1 acted as a potential regulator of radioresistance of PCa, providing a promising therapeutic target for PCa.
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Affiliation(s)
- Minhua Hu
- Department of Nursing College, Xi’an Medical University, Xi’an, 710021 Shaanxi Province China
| | - Jincheng Yang
- Department of Urology Surgery, The First People’s Hospital of Yinchuan, No. 4, Liqun West Street, Xingqing District, Yinchuan, 750004 Ningxia China
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16
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Lei Y, Chen L, Zhang G, Shan A, Ye C, Liang B, Sun J, Liao X, Zhu C, Chen Y, Wang J, Zhang E, Deng L. MicroRNAs target the Wnt/β‑catenin signaling pathway to regulate epithelial‑mesenchymal transition in cancer (Review). Oncol Rep 2020; 44:1299-1313. [PMID: 32700744 PMCID: PMC7448411 DOI: 10.3892/or.2020.7703] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Accepted: 06/24/2020] [Indexed: 12/11/2022] Open
Abstract
Epithelial‑mesenchymal transition (EMT), during which cancer cells lose the epithelial phenotype and gain the mesenchymal phenotype, has been verified to result in tumor migration and invasion. Numerous studies have shown that dysregulation of the Wnt/β‑catenin signaling pathway gives rise to EMT, which is characterized by nuclear translocation of β‑catenin and E‑cadherin suppression. Wnt/β‑catenin signaling was confirmed to be affected by microRNAs (miRNAs), several of which are down‑ or upregulated in metastatic cancer cells, indicating their complex roles in Wnt/β‑catenin signaling. In this review, we demonstrated the targets of various miRNAs in altering Wnt/β‑catenin signaling to promote or inhibit EMT, which may elucidate the underlying mechanism of EMT regulation by miRNAs and provide evidence for potential therapeutic targets in the treatment of invasive tumors.
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Affiliation(s)
- Yuhe Lei
- Department of Pharmacy, Shenzhen Hospital of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518000, P.R. China
| | - Lei Chen
- Department of Pharmacy, Shenzhen Hospital of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518000, P.R. China
| | - Ge Zhang
- Department of Big Data Research of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong 510120, P.R. China
| | - Aiyun Shan
- Department of Pharmacy, Shenzhen Hospital of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518000, P.R. China
| | - Chunfeng Ye
- Department of Pediatrics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Bin Liang
- Formula Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China
| | - Jiayu Sun
- Department of Pharmacy, Shenzhen Hospital of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518000, P.R. China
| | - Xin Liao
- Department of Pharmacy, Shenzhen Hospital of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518000, P.R. China
| | - Changfeng Zhu
- Department of Pharmacy, Shenzhen Hospital of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518000, P.R. China
| | - Yueyue Chen
- Formula Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China
| | - Jing Wang
- Formula Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China
| | - Enxin Zhang
- Department of Oncology, Shenzhen Hospital of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518000, P.R. China
| | - Lijuan Deng
- Formula Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China
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17
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Zhao JB, Xue JF, Zhang WZ, Ren YL, Yan DM. Long Noncoding RNA FGD5-AS1 Promotes Glioma Cell Proliferation, Migration and Invasion by Regulating wnt/β-Catenin Pathway. Cancer Manag Res 2020; 12:6187-6193. [PMID: 32801867 PMCID: PMC7398887 DOI: 10.2147/cmar.s250284] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Accepted: 05/17/2020] [Indexed: 12/15/2022] Open
Abstract
Purpose To investigate the specific function of long noncoding RNA FGD5 antisense RNA 1 (lncRNA FGD5-AS1) in glioma. Materials and Methods The level of FGD5-AS1 was detected in clinical samples and cell lines by qRT-PCR. Small interfering RNA (siRNA) of FGD5-AS1 or scramble siRNA was transfected into U87 cell lines to examine the role of FGD5-AS1 on glioma development. The proliferation of glioma cells was tested by Cell Counting Kit-8 (CCK-8), the migration and invasion of glioma cells were tested by transwell assay without matrigel or with matrigel. Western blot was used to detect the protein expression, and XAV-939 was used to inhibit wnt/β-catenin pathway. The effect of FGD5-AS1 on tumorigenesis of glioma was confirmed by xenograft nude mice model. Results FGD5-AS1 was significantly increased in glioma tissues and cells. Loss of FGD5-AS1 inhibited the proliferation, migration and invasion of U87 cells. Furthermore, overexpression of FGD5-AS1 increased the mRNA and protein levels of β-catenin and cyclin D1. Blocking of wnt/β-catenin using XAV-939 reversed the promotion role of FGD3-AS1 on glioma cells’ migration and invasion. The in vivo tumor growth assay showed that FGD3-AS1 accelerated glioma tumorigenesis with activating wnt/β-catenin pathway. Conclusion Our research emphasized FGD5-AS1 acting as an oncogene by regulating wnt/β-catenin signaling pathway, thus providing some novel experimental basis for clinical treatment of glioma.
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Affiliation(s)
- Jun Bo Zhao
- Department of Neurosurgery, Jiaozuo People's Hospital, Jiaozuo 454000, Henan Province, People's Republic of China
| | - Jun Feng Xue
- Department of Neurosurgery, Jiaozuo People's Hospital, Jiaozuo 454000, Henan Province, People's Republic of China
| | - Wu Zhong Zhang
- Department of Neurosurgery, Jiaozuo People's Hospital, Jiaozuo 454000, Henan Province, People's Republic of China
| | - Yong Lu Ren
- Department of Neurosurgery, Jiaozuo People's Hospital, Jiaozuo 454000, Henan Province, People's Republic of China
| | - Dong Ming Yan
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, People's Republic of China
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18
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Xiao B, Zhang X, Li X, Zhao Z. Circ_001569 regulates FLOT2 expression to promote the proliferation, migration, invasion and EMT of osteosarcoma cells through sponging miR-185-5p. Open Life Sci 2020; 15:476-487. [PMID: 33817236 PMCID: PMC7874578 DOI: 10.1515/biol-2020-0050] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 04/16/2020] [Accepted: 04/23/2020] [Indexed: 12/19/2022] Open
Abstract
Osteosarcoma (OS) is a common malignant tumor in the world. Circular RNAs are endogenous non-coding RNAs that have been linked to the development of cancer. However, the role of circ_001569 in OS progression is still unclear. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of circ_001569, microRNA-185-5p (miR-185-5p) and flotillin-2 (FLOT2). The abilities of cell proliferation, migration and invasion were evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and Transwell assays, respectively. Also, western blot analysis was performed to assess the levels of epithelial-mesenchymal transition (EMT)-related proteins and FLOT2 protein. Besides, the dual-luciferase reporter assay was used to verify the interactions among circ_001569, miR-185-5p and FLOT2. Circ_001569 expression was increased in OS tissues and cells, and its knockdown reduced the proliferation, migration, invasion and EMT of OS cells. MiR-185-5p could interact with circ_001569. Inhibition of miR-185-5p could recover the suppression effects of silenced-circ_001569 on the proliferation and metastasis of OS cells. Furthermore, FLOT2 was a target of miR-185-5p. Overexpressed FLOT2 could restore the inhibition effects of miR-185-5p mimic on the proliferation and metastasis of OS cells. Also, FLOT2 expression was regulated by circ_001569 and miR-185-5p. In addition, circ_001569 knockdown also reduced the OS tumor growth in vivo. Circ_001569 might act as an oncogene in OS progression by regulating the miR-185-5p/FLOT2 axis, which provided a reliable new approach for the treatment of OS patients.
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Affiliation(s)
- Bin Xiao
- Department of Orthopaedic, Second People’s Hospital of Gansu Province, No. 1 Hezheng West Street, Chengguan District, Lanzhou City, Gansu Province, 730000, China
| | - Xusheng Zhang
- Department of General Surgery, Second People’s Hospital of Gansu Province, 730000, Lanzhou, Gansu, China
| | - Xiaojuan Li
- Department of Endocrine, Second People’s Hospital of Gansu Province, 730000, Lanzhou, Gansu, China
| | - Zhipeng Zhao
- Department of Orthopaedic, Second People’s Hospital of Gansu Province, No. 1 Hezheng West Street, Chengguan District, Lanzhou City, Gansu Province, 730000, China
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19
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Sabo AA, Birolo G, Naccarati A, Dragomir MP, Aneli S, Allione A, Oderda M, Allasia M, Gontero P, Sacerdote C, Vineis P, Matullo G, Pardini B. Small Non-Coding RNA Profiling in Plasma Extracellular Vesicles of Bladder Cancer Patients by Next-Generation Sequencing: Expression Levels of miR-126-3p and piR-5936 Increase with Higher Histologic Grades. Cancers (Basel) 2020; 12:cancers12061507. [PMID: 32527011 PMCID: PMC7352804 DOI: 10.3390/cancers12061507] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2020] [Revised: 06/02/2020] [Accepted: 06/04/2020] [Indexed: 12/24/2022] Open
Abstract
Bladder cancer (BC) is the tenth most frequent cancer worldwide. Due to the need for recurrent cystoscopies and the lack of non-invasive biomarkers, BC is associated with a high management burden. In this respect, small non-coding RNAs (sncRNAs) have been investigated in urine as possible biomarkers for BC, but in plasma their potential has not yet been defined. The expression levels of sncRNAs contained in plasma extracellular vesicles (EVs) from 47 men with BC and 46 healthy controls were assessed by next-generation sequencing. The sncRNA profiles were compared with urinary profiles from the same subjects. miR-4508 resulted downregulated in plasma EVs of muscle-invasive BC patients, compared to controls (adj-p = 0.04). In World Health Organization (WHO) grade 3 (G3) BC, miR-126-3p was upregulated both in plasma EVs and urine, when compared to controls (for both, adj-p < 0.05). Interestingly, two sncRNAs were associated with the risk class: miR-4508 with a downward trend going from controls to high risk BC, and piR-hsa-5936 with an upward trend (adj-p = 0.04 and adj-p = 0.05, respectively). Additionally, BC cases with low expression of miR-185-5p and miR-106a-5p or high expression of miR-10b-5p showed shorter survival (adj-p = 0.0013, adj-p = 0.039 and adj-p = 0.047, respectively). SncRNAs from plasma EVs could be diagnostic biomarkers for BC, especially in advanced grade.
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Affiliation(s)
- Alexandru A. Sabo
- Klinikum Stuttgart, Olgahospital, Zentrum für Kinder, Jugend und Frauenmedizin, Pediatrics 2 (General and Special Pediatrics), 70174 Stuttgart, Germany;
- Department of Pediatrics, Marie Curie Emergency Clinical Hospital for Children, 041434 Bucharest, Romania
| | - Giovanni Birolo
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (G.B.); (S.A.); (A.A.); (G.M.)
| | - Alessio Naccarati
- Italian Institute for Genomic Medicine (IIGM) 10060 Candiolo, Italy; (A.N.); (P.V.)
- Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy
| | - Mihnea P. Dragomir
- Department of Surgery, Fundeni Clinical Hospital, Carol Davila University of Medicine and Pharmacy, 022328 Bucharest, Romania;
| | - Serena Aneli
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (G.B.); (S.A.); (A.A.); (G.M.)
| | - Alessandra Allione
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (G.B.); (S.A.); (A.A.); (G.M.)
| | - Marco Oderda
- Department of Surgical Sciences, University of Turin and Città della Salute e della Scienza, 10126 Turin, Italy; (M.O.); (M.A.); (P.G.)
| | - Marco Allasia
- Department of Surgical Sciences, University of Turin and Città della Salute e della Scienza, 10126 Turin, Italy; (M.O.); (M.A.); (P.G.)
| | - Paolo Gontero
- Department of Surgical Sciences, University of Turin and Città della Salute e della Scienza, 10126 Turin, Italy; (M.O.); (M.A.); (P.G.)
| | | | - Paolo Vineis
- Italian Institute for Genomic Medicine (IIGM) 10060 Candiolo, Italy; (A.N.); (P.V.)
- MRC-HPA Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK
| | - Giuseppe Matullo
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (G.B.); (S.A.); (A.A.); (G.M.)
| | - Barbara Pardini
- Italian Institute for Genomic Medicine (IIGM) 10060 Candiolo, Italy; (A.N.); (P.V.)
- Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy
- Correspondence:
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20
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Cao C, Zhang J, Yang C, Xiang L, Liu W. Silencing of long noncoding RNA UCA1 inhibits colon cancer invasion, migration and epithelial-mesenchymal transition and tumour formation by upregulating miR-185-5p in vitro and in vivo. Cell Biochem Funct 2020; 38:176-184. [PMID: 31989667 DOI: 10.1002/cbf.3454] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Revised: 10/09/2019] [Accepted: 10/21/2019] [Indexed: 12/15/2022]
Abstract
Colon cancer is the third most common malignancy in the world. Long-chain noncoding RNA urothelial carcinoma-associated 1 (UCA1) was abnormally expressed in colon cancer and participated in colon cancer by regulating multiple miRNAs. This study further explored the molecular mechanism of UCA1 in the development of colon cancer from both in vitro and in vivo. The results showed that UCA1 was highly expressed in colon cancer cells, while miR-185-5p was low expressed. Bioinformatics analysis showed that miR-185-5p was a target of UCA1, while MAPK14 was a target of miR-185-5p. Knockdown of UCA1 with shRNA (sh-UCA1) resulted in a significant increase in miR-185-5p and a significant decrease in MAPK14. In addition, sh-UCA1 inhibited invasion, migration and epithelial-mesenchymal transformation of colon cancer cells. Western blotting also showed that sh-UCA1 inactivated the MAPKAPK2/HSP27 pathway. Furthermore, animal studies have revealed that sh-UCA1 inhibited tumour formation in vivo and improved the survival rate of mice. Collectively, these results suggest that silencing UCA1 may inhibit the carcinogenesis and metastasis of colon cancer in vitro and in vivo by modulating miR-185-5p/MAPK14/MAPKAPK2/HSP27 axis. SIGNIFICANCE OF THE STUDY: Colon cancer is the third largest malignant tumour worldwide. This study elucidated the role of urothelial carcinoma-associated 1 (UCA1) in colon cancer cells and its molecular mechanism. The present study suggests that silencing UCA1 may inhibit the invasion, migration, epithelial-mesenchymal transformation and tumour formation of colon cancer by upregulating miR-185-5p in vitro and in vivo. In summary, this study provides a new strategy for targeted therapy of colon cancer.
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Affiliation(s)
- Chen Cao
- Department of Hyroid and Breast Surgery, West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Junhui Zhang
- Department of Hyroid and Breast Surgery, West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Chuanhua Yang
- Department of Hyroid and Breast Surgery, West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Lili Xiang
- Department of Hyroid and Breast Surgery, West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Wenneng Liu
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
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21
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LncRNA PCAT6 promotes tumor progression in osteosarcoma via activation of TGF-β pathway by sponging miR-185-5p. Biochem Biophys Res Commun 2020; 521:463-470. [DOI: 10.1016/j.bbrc.2019.10.136] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Accepted: 10/18/2019] [Indexed: 02/07/2023]
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22
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Yan H, Zhu C, Zhang L. Kinesin family member 18B: A contributor and facilitator in the proliferation and metastasis of cutaneous melanoma. J Biochem Mol Toxicol 2019; 33:e22409. [PMID: 31617652 DOI: 10.1002/jbt.22409] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Revised: 09/16/2019] [Accepted: 10/01/2019] [Indexed: 12/11/2022]
Abstract
Melanoma is the most aggressive type of cutaneous tumor and the occurrence of metastasis makes it resistant to almost all available treatment and becomes incorrigible. Hence, identifying metastasis-related biomarkers and effective therapeutic targets will assist in preventing metastasis and ameliorating cutaneous melanoma. In our present study, we reported kinesin family member 18B (KIF18B) as a novel contributor in cutaneous melanoma proliferation and metastasis, and it was found to be of great significance in predicting the prognosis of cutaneous melanoma patients. Bioinformatics analysis based on ONCOMINE, The Cancer Genome Atlas, and Genotype-Tissue Expression database revealed that KIF18B was highly expressed in cutaneous melanoma and remarkably correlated with unfavorable clinical outcomes. Consistently, the results of the quantitative real-time polymerase chain reaction exhibited that the expression of KIF18B was significantly higher in cutaneous melanoma cell lines than that in normal cells. In vitro, biological assays found that knockdown of KIF18B in cutaneous melanoma cells noticeably repressed cell proliferation, migration, and invasion, while inducing cell apoptosis. Moreover, the protein expression of E-cadherin was enhanced while the expression of N-cadherin, vimentin, and Snail was decreased in M14 cells after knocking down KIF18B. In addition, the phosphorylation of phosphoinositide 3-kinase (PI3K) and extracellular-signal-regulated kinase (ERK) was significantly suppressed in M14 cells with silenced KIF18B. Above all, our results indicated that the repression of cutaneous melanoma cell migration and proliferation caused by KIF18B depletion suggested an oncogenic role of KIF18B in cutaneous melanoma, which acts through modulating epithelial-mesenchymal transition and ERK/PI3K pathway.
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Affiliation(s)
- Hongmei Yan
- Department of Dermatology, School of Clinical Medicine, Shandong University, Jinan, Shandong, China
- Department of Dermatology, The Fourth Hospital of Jinan, Jinan, Shandong, China
| | - Changyou Zhu
- Department of Internal Medicine-Cardiovascular, Affiliated Jinan Third Hospital of Jining Medical University, Jinan, Shandong, China
| | - Li Zhang
- Department of Dermatology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China
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23
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Li G, Liu T, Zhang B, Chen W, Ding Z. Genome-wide identification of a competing endogenous RNA network in cholangiocarcinoma. J Cell Biochem 2019; 120:18995-19003. [PMID: 31270845 PMCID: PMC6771781 DOI: 10.1002/jcb.29222] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Accepted: 05/14/2019] [Indexed: 12/15/2022]
Abstract
Cholangiocarcinoma (CCA) is the second widespread liver tumor with relatively poor survival. Increasing evidence in recent studies showed long noncoding RNAs (lncRNAs) exert a crucial impact on the development and progression of CCA based on the mechanism of competing endogenous RNAs (ceRNAs). However, functional roles and regulatory mechanisms of lncRNA-regulated ceRNA in CCA, are only partially understood. The expression profile of messenger RNAs (mRNAs), lncRNAs, and microRNAs (miRNAs) downloaded from The Cancer Genome Atlas were comprehensively investigated. Differential expression of these three types of RNA between CCA and corresponding precancerous tissues were screened out for further analysis. On the basis of interactive information generated from miRDB, miRTarBase, TargetScan, and miRcode public databases, we then constructed an mRNA-miRNA-lncRNA regulatory network. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses were conducted to identify the biological function of the ceRNA network involved in CCA. As a result, 2883 mRNAs, 136 miRNAs, and 993 lncRNAs were screened out as differentially expressed RNAs in CCA. In addition, a ceRNA network in CCA was constructed, composing of 50 up and 27 downregulated lncRNAs, 14 up and 7 downregulated miRNAs, 29 up and 25 downregulated mRNAs. Finally, gene set enrichment and pathway analysis indicated our CCA-specific ceRNA network was related with cancer-related pathway and molecular function. In conclusion, our research identified a novel lncRNA-related ceRNA network in CCA, which might act as a potential therapeutic target for patients with CCA.
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Affiliation(s)
- Ganxun Li
- Department of SurgeryHepatic Surgery CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Tongtong Liu
- Department of AnesthesiologyTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Bixiang Zhang
- Department of SurgeryHepatic Surgery CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Weixun Chen
- Department of SurgeryHepatic Surgery CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Zeyang Ding
- Department of SurgeryHepatic Surgery CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
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The long non-coding RNA, urothelial carcinoma associated 1, promotes cell growth, invasion, migration, and chemo-resistance in glioma through Wnt/β-catenin signaling pathway. Aging (Albany NY) 2019; 11:8239-8253. [PMID: 31596734 PMCID: PMC6814589 DOI: 10.18632/aging.102317] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Accepted: 09/21/2019] [Indexed: 02/07/2023]
Abstract
The long non-coding RNA, urothelial carcinoma associated 1 (UCA1) has been demonstrated to play important roles in various types of cancers. This study investigated the functional role of UCA1 in glioma and explored the underlying molecular mechanisms. UCA1 was found to be highly up-regulated in glioma cells, and knock-down of UCA1 inhibited cell growth, invasion and migration, and also induced apoptosis in glioma cells. On the other hand, overexpression of UCA1 promoted cell proliferation, cell invasion and migration in glioma cells. Knock-down of UCA1 suppressed the activity of Wnt/β-catenin signaling, and treatment with lithium chloride restored the inhibitory effect of UCA1 knock-down on cell invasion and migration. More importantly, the aberrant expression of UCA1 was associated with chemo-resistance to cisplatin and temozolomide in glioma cells via interacting with Wnt/β-catenin signaling. In vivo studies showed that overexpression of UCA1 promoted the in vivo tumor growth of U87 cells in the nude mice. Clinically, UCA1 was found to be up-regulated in glioma tissues and higher expression level of UCA1 was correlated with poor survival in patients with glioma. Taken together, our results showed that UCA1 had a functional role in the regulation of glioma cell growth, invasion and migration, and chemo-resistance possibly via Wnt/β-catenin signaling pathway.
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25
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UCA1 long non-coding RNA: An update on its roles in malignant behavior of cancers. Biomed Pharmacother 2019; 120:109459. [PMID: 31585301 DOI: 10.1016/j.biopha.2019.109459] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2019] [Revised: 09/06/2019] [Accepted: 09/12/2019] [Indexed: 12/24/2022] Open
Abstract
The lncRNA urothelial carcinoma-associated 1 (UCA1) is a 1.4 kb long transcript which has been firstly recognized in human bladder cancer cell line. Subsequent studies revealed its over-expression in a wide array of human cancer cell lines and patients' samples. In addition to conferring malignant phenotype to cells, it enhances resistance to conventional anti-cancer drugs. Moreover, transcript levels of this lncRNA have been regarded as diagnostic markers in several cancer types including gastric, bladder and liver cancers. The underlying mechanism of its participation in carcinogenesis has been identified in some cancer types. Sponging tumor suppressor miRNAs, interacting with cancer-promoting signaling pathways and enhancing cell cycle progression are among these mechanisms. Although few studies have shown anti-carcinogenic properties for this lncRNA, the bulk of evidence supports its oncogenic roles. In the current study, we have reviewed the current literature on the role of UCA1 in the carcinogenic process based on the results of in vitro studies, investigations in animal models and assessment of UCA1 expression in clinical samples.
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26
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Xuan W, Yu H, Zhang X, Song D. Crosstalk between the lncRNA UCA1 and microRNAs in cancer. FEBS Lett 2019; 593:1901-1914. [PMID: 31166011 DOI: 10.1002/1873-3468.13470] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Revised: 05/28/2019] [Accepted: 05/29/2019] [Indexed: 12/11/2022]
Abstract
Long non-coding RNAs (lncRNAs) are a major subset of highly conserved non-coding RNAs (ncRNAs) that consist of at least 200 nucleotides and have limited protein-coding potential. Cumulative data have shown that lncRNAs are deregulated in many types of cancer and may control pathophysiological processes of cancer at various levels, including transcription, post-transcription and translation. Recently, lncRNAs have been demonstrated to interact with microRNAs (miRNAs), another major subset of ncRNAs, which regulate physiological and pathological processes by inhibiting target mRNA translation or promoting mRNA degradation. The lncRNA urothelial carcinoma-associated 1 (UCA1) has recently gained much attention as it is overexpressed in many types of cancer and is involved in carcinogenesis. Here, we review the crosstalk between UCA1 and miRNAs during the pathogenesis of cancer, with a focus on cancer-cell proliferation, invasion, drug resistance, and metabolism.
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Affiliation(s)
- Wei Xuan
- Department of Hepatopancreaticobiliary Surgery, China-Japan Union Hospital, Jilin University, Changchun, China
| | - Hongyu Yu
- Department of Nephrology, Second Hospital of Jilin University, Changchun, China
| | - Xiaoling Zhang
- The First Hospital and Institute of Immunology, Jilin University, Changchun, China
| | - Dandan Song
- Department of Clinical Laboratory, Second Hospital of Jilin University, Changchun, China
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27
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Pei S, Chen J, Lu J, Hu S, Jiang L, Lei L, Ouyang Y, Fu C, Ding Y, Li S, Kang L, Huang L, Xiang H, Xiao R, Zeng Q, Huang J. The Long Noncoding RNA UCA1 Negatively Regulates Melanogenesis in Melanocytes. J Invest Dermatol 2019; 140:152-163.e5. [PMID: 31276678 DOI: 10.1016/j.jid.2019.04.029] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Revised: 04/08/2019] [Accepted: 04/14/2019] [Indexed: 02/09/2023]
Abstract
The long noncoding RNA UCA1 was first discovered in bladder cancer and is known to regulate the proliferation and migration of melanoma. However, its role in melanogenesis is unclear. In this study, we aimed to explore the role and mechanism of UCA1 in melanogenesis. Our findings showed that the expression of UCA1 was negatively correlated with melanin content in melanocytes and pigmented nevus. Overexpression of UCA1 in melanocytes decreased melanin content and the expression of melanogenesis-related genes, whereas knockdown of UCA1 in melanocytes had the opposite effect. High-throughput sequencing revealed that microphthalmia-associated transcription factor (MITF), an important transcription factor affecting melanogenesis, was also negatively correlated with the expression of UCA1. Furthermore, the transcription factor CRE-binding protein (CREB), which promotes MITF expression, was negatively regulated by UCA1. The cAMP/protein kinase A (PKA), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) signaling pathways, which are upstream of the CREB/MITF/melanogenesis axis, were activated or inhibited in response to silencing or enhancing UCA1 expression, respectively. In addition, enhanced UCA1 expression downregulates the expression of melanogenesis-related genes induced by UVB in melanocytes. In conclusion, UCA1 may negatively regulate the CREB/MITF/melanogenesis axis through inhibiting the cAMP/PKA, ERK, and JNK signaling pathways in melanocytes. UCA1 may be a potential therapeutic target for the treatment of pigmented skin diseases.
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Affiliation(s)
- Shiyao Pei
- Department of Dermatology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Jing Chen
- Department of Dermatology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Jianyun Lu
- Department of Dermatology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Shuanghai Hu
- Department of Dermatology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Ling Jiang
- Department of Dermatology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Li Lei
- Department of Dermatology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yujie Ouyang
- Department of Dermatology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Chuhan Fu
- Department of Dermatology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yufang Ding
- Department of Dermatology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Si Li
- Department of Dermatology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Liyang Kang
- Department of Dermatology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Lihua Huang
- Central Laboratory, Third Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Hong Xiang
- Central Laboratory, Third Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Rong Xiao
- Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Qinghai Zeng
- Department of Dermatology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
| | - Jinhua Huang
- Department of Dermatology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
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28
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Horita K, Kurosaki H, Nakatake M, Ito M, Kono H, Nakamura T. Long noncoding RNA UCA1 enhances sensitivity to oncolytic vaccinia virus by sponging miR-18a/miR-182 and modulating the Cdc42/filopodia axis in colorectal cancer. Biochem Biophys Res Commun 2019; 516:831-838. [PMID: 31262449 DOI: 10.1016/j.bbrc.2019.06.125] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Accepted: 06/22/2019] [Indexed: 12/11/2022]
Abstract
The promising anti-tumor effects of oncolytic vaccinia virus (OVV) have been demonstrated. Further, we previously showed that long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) enhances OVV cell-to-cell spread via the activation of Cdc42 in ovarian cancer. However, its role in other cancer types and the molecular mechanism underlying its effects remain to be explored. In this study, we first demonstrated that UCA1 upregulates OVV cell-to-cell spread but not its binding, entry, and replication in colorectal cancer cells. Functional analysis indicated that Cdc42 activation and filopodia formation play an important role in this process. Moreover, expression analysis of various miRNAs suggested that UCA1 inhibits both miR-18a and miR-182, thereby promoting Cdc42 activation, which in turn, regulates OVV cell-to-cell spread. Furthermore, UCA1 was found to modulate tumor malignancy, drug resistance, and sensitivity to OVV via different miRNAs in colorectal cancer. These findings indicate that a three-marker panel, which includes UCA1 expression, Cdc42 activation, and filopodia formation, could potentially be used to predict the therapeutic effect of OVV in colorectal cancer.
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Affiliation(s)
- Kosuke Horita
- Division of Molecular Medicine, Department of Biomedical Science, Graduate School of Medical Sciences, Tottori University, 86 Nishi-cho, Yonago, 683-8503, Japan
| | - Hajime Kurosaki
- Division of Molecular Medicine, Department of Biomedical Science, Graduate School of Medical Sciences, Tottori University, 86 Nishi-cho, Yonago, 683-8503, Japan
| | - Motomu Nakatake
- Division of Molecular Medicine, Department of Biomedical Science, Graduate School of Medical Sciences, Tottori University, 86 Nishi-cho, Yonago, 683-8503, Japan
| | - Mai Ito
- Division of Molecular Medicine, Department of Biomedical Science, Graduate School of Medical Sciences, Tottori University, 86 Nishi-cho, Yonago, 683-8503, Japan
| | - Hiromichi Kono
- Division of Molecular Medicine, Department of Biomedical Science, Graduate School of Medical Sciences, Tottori University, 86 Nishi-cho, Yonago, 683-8503, Japan
| | - Takafumi Nakamura
- Division of Molecular Medicine, Department of Biomedical Science, Graduate School of Medical Sciences, Tottori University, 86 Nishi-cho, Yonago, 683-8503, Japan.
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McCoach CE, Bivona TG. Engineering Multidimensional Evolutionary Forces to Combat Cancer. Cancer Discov 2019; 9:587-604. [PMID: 30992280 PMCID: PMC6497542 DOI: 10.1158/2159-8290.cd-18-1196] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Revised: 12/28/2018] [Accepted: 01/29/2019] [Indexed: 02/07/2023]
Abstract
With advances in technology and bioinformatics, we are now positioned to view and manage cancer through an evolutionary lens. This perspective is critical as our appreciation for the role of tumor heterogeneity, tumor immune compartment, and tumor microenvironment on cancer pathogenesis and evolution grows. Here, we explore recent knowledge on the evolutionary basis of cancer pathogenesis and progression, viewing tumors as multilineage, multicomponent organisms whose growth is regulated by subcomponent fitness relationships. We propose reconsidering some current tenets of the cancer management paradigm in order to take better advantage of crucial fitness relationships to improve outcomes of patients with cancer. SIGNIFICANCE: Tumor and tumor immune compartment and microenvironment heterogeneity, and their evolution, are critical disease features that affect treatment response. The impact and interplay of these components during treatment are viable targets to improve clinical response. In this article, we consider how tumor cells, the tumor immune compartment and microenvironment, and epigenetic factors interact and also evolve during treatment. We evaluate the convergence of these factors and suggest innovative treatment concepts that leverage evolutionary relationships to limit tumor growth and drug resistance.
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Affiliation(s)
- Caroline E McCoach
- Department of Medicine, University of California, San Francisco, California.
- Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California
| | - Trever G Bivona
- Department of Medicine, University of California, San Francisco, California.
- Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California
- Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California
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30
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Liu X, Huang Z, Qian W, Zhang Q, Sun J. Silence of lncRNA UCA1 rescues drug resistance of cisplatin to non-small-cell lung cancer cells. J Cell Biochem 2019; 120:9243-9249. [PMID: 30652341 DOI: 10.1002/jcb.28200] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Accepted: 11/15/2018] [Indexed: 01/02/2023]
Abstract
The aim of this study was to investigate the effect of long noncoding RNA (lncRNA) urogenital carcinoma antigen 1 (UCA1) on drug resistance in A549/DDP cell and explore its underlying mechanism. The inhibition rate and IC 50 of DDP were detected in A549 and A549/DDP cells by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide assay. The expression of lncRNA UCA1 was measured in A549 and A549/DDP cells by quantitative real-time polymerase chain reaction. The expressions of N-cadherin, E-cadherin, vimentin, and Snail were detected in A549 and A549/DDP cells by Western blot analysis. Results showed that the IC 50 of DDP was 16.20 ± 2.27 μmol/L and 69.72 ± 4.83 μmol/L in A549 and A549/ DDP cells, respectively. Compared with the A549 group, the expressions of N-cadherin, vimentin, and Snail was significantly upregulated in A549/DDP group, but E-cadherin was significantly downregulated. Compared with the shCon group, the abundance of N-cadherin, vimentin, and Snail was significantly downregulated in short hairpin RNA UCA1 (shUCA1) group, while E-cadherin was significantly upregulated. Cell migration and invasion were significantly suppressed and IC 50 was reversed to 16.20 ± 2.27 μmol/L in the shUCA1 group. Silencing lncRNA UCA1 inhibited the migration and invasion of A549/DDP cells and reversed the resistance of A549/DDP cells to DDP. The mechanism might be related to downregulation of epithelial-mesenchymal transition, which will provide a new direction for the treatment of non-small-cell lung cancer with cisplatin.
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Affiliation(s)
- Xiaojing Liu
- Department of Respiratory and Critical Care Medicine, The Fourth Affiliated Hospital of Nanchang University, Nanchang, China
| | - Zhisheng Huang
- Department of Respiratory and Critical Care Medicine, The Fourth Affiliated Hospital of Nanchang University, Nanchang, China
| | - Wei Qian
- Department of Respiratory and Critical Care Medicine, The Fourth Affiliated Hospital of Nanchang University, Nanchang, China
| | - Qing Zhang
- Department of Respiratory and Critical Care Medicine, The Fourth Affiliated Hospital of Nanchang University, Nanchang, China
| | - Jian Sun
- Department of Respiratory and Critical Care Medicine, The Fourth Affiliated Hospital of Nanchang University, Nanchang, China
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Xu C, Li Z, He T, Yuan B, Ding B. Retracted Article: Long noncoding RNA PTPRG-AS1 regulates growth of glioma cells by sponging miR-185-5p. RSC Adv 2019; 9:10870-10880. [PMID: 35515299 PMCID: PMC9062606 DOI: 10.1039/c8ra09546a] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Accepted: 03/14/2019] [Indexed: 12/16/2022] Open
Abstract
Previous studies have found that long noncoding RNA (lncRNA) protein tyrosine phosphatase, receptor type, G, antisense (PTPRG-AS1) was upregulated in glioma cells. Our study aimed to explore the detailed molecular mechanisms of PTPRG-AS1 involved in glioma progression. qRT-PCR assay was performed to measure the expressions of PTPRG-AS1 and microRNA-185-5p (miR-185-5p). Cell viability, migration, invasion, and apoptosis were determined by CCK-8 assay, colony formation assay, transwell assay, and flow cytometry assay. Autophagy was evaluated using GFP-LC3 puncta analysis and western blot. Luciferase reporter and RIP assays were employed to explore the association between PTPRG-AS1 and miR-185-5p. Our data showed PTPRG-AS1 was upregulated in glioma cells and tissues. Besides, high expression of PTPRG-AS1 was positively associated with a low survival rate. Upregulation of PTPRG-AS1 promoted proliferation, migration, invasion, colony formations, and autophagy, and inhibited cell apoptosis in U373-MG cells. By contrast, PTPRG-AS1 downregulation had the inverse effect in SHG44 cells. PTPRG-AS1 negatively regulated the expression of miR-185-5p in U373-MG and SHG44 cells and the expression of miR-185-5p was decreased in glioma tissues and cells. In addition, miR-185-5p overexpression suppressed proliferation, metastasis, colony formations, and autophagy, while inducing cell apoptosis in SHG44 cells. As expected, miR-185-5p depletion exhibited the inverse effect in U373-MG cells. Enhanced expression of miR-185-5p attenuated the effect of PTPRG-AS1 upregulation on U373-MG cells, while silencing of miR-185-5p undermined the effect of downregulation of PTPRG-AS1 on SHG44 cells. Our data disclosed that LncRNA PTPRG-AS1 was upregulated in glioma cells and tissues. PTPRG-AS1 regulated glioma proliferation, invasion, migration, apoptosis and autophagy by sponging miR-185-5p in vitro. A new signaling pathway PTPRG-AS1/miR-185-5p was first observed in glioma. Previous studies have found that long noncoding RNA (lncRNA) protein tyrosine phosphatase, receptor type, G, antisense (PTPRG-AS1) was upregulated in glioma cells.![]()
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Affiliation(s)
- Chenyang Xu
- Department of Neurosurgery
- Huaihe Hospital of Henan University
- Kaifeng
- China
| | - Zhenjiang Li
- Department of Neurosurgery
- Huaihe Hospital of Henan University
- Kaifeng
- China
| | - Tao He
- Department of Neurosurgery
- Huaihe Hospital of Henan University
- Kaifeng
- China
| | - Bingjian Yuan
- Department of Neurosurgery
- Huaihe Hospital of Henan University
- Kaifeng
- China
| | - Bingqian Ding
- Department of Neurosurgery
- Huaihe Hospital of Henan University
- Kaifeng
- China
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32
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Shen F, Chang H, Gao G, Zhang B, Li X, Jin B. Long noncoding RNA FOXD2-AS1 promotes glioma malignancy and tumorigenesis via targeting miR-185-5p/CCND2 axis. J Cell Biochem 2018; 120:9324-9336. [PMID: 30520141 DOI: 10.1002/jcb.28208] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 11/15/2018] [Indexed: 12/30/2022]
Abstract
Glioma is the most aggressive malignant tumor in the adult central nervous system. Abnormal long noncoding RNA (lncRNA) FOXD2-AS1 expression was associated with tumor development. However, the possible role of FOXD2-AS1 in the progression of glioma is not known. In the present study, we used in vitro and in vivo assays to investigate the effect of abnormal expression of FOXD2-AS1 on glioma progression and to explore the mechanisms. FOXD2-AS1 was upregulated in glioma tissue, cells, and sphere subpopulation. Upregulation of FOXD2-AS1 was correlated with poor prognosis of glioma. Downregulation of FOXD2-AS1 decreased cell proliferation, migration, invasion, stemness, and epithelial-mesenchymal transition (EMT) in glioma cells and inhibited tumor growth in transplanted tumor. We also revealed that FOXD2-AS1 was mainly located in cytoplasm and microRNA (miR)-185-5p both targeted FOXD2-AS1 and CCND2 messenger RNA (mRNA) 3'-untranslated region (3'-UTR). miR-185-5p was downregulated in glioma tissue, cells, and sphere subpopulation. Downregulation of miR-185-5p was closely correlated with poor prognosis of glioma patients. In addition, miR-185-5p mimics decreased cell proliferation, migration, invasion, stemness, and EMT in glioma cells. CCND2 was upregulated in glioma tissue, cells, and sphere subpopulation. Upregulation of CCND2 was closely correlated with poor prognosis of glioma patients. CCND2 knockdown decreased cell proliferation, migration, invasion, and EMT in glioma cells. In glioma tissues, CCND2 expression was negatively associated with miR-185-5p, but positively correlated with FOXD2-AS1. FOXD2-AS1 knockdown and miR-185-5p mimics decreased CCND2 expression. Inhibition of miR-185-5p suppressed FOXD2-AS1 knockdown-induced decrease of CCND2 expression. Overexpression of CCND2 suppressed FOXD2-AS1 knockdown-induced inhibition of glioma malignancy. Taken together, our findings highlight the FOXD2-AS1/miR-185-5p/CCND2 axis in the glioma development.
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Affiliation(s)
- Fazheng Shen
- Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, China
| | - Haigang Chang
- Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, China
| | - Guojun Gao
- Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, China
| | - Bin Zhang
- Department of The Clinical Laboratory, The Clinical Laboratory, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, China
| | - Xiangsheng Li
- Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, China
| | - Baozhe Jin
- Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, China
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