title: MiR-199a-5p suppresses tumorigenesis by targeting clathrin heavy chain in hepatocellular carcinoma.
abstract: The deregulation of microRNA (miRNA) is frequently associated with a variety of cancers, including hepatocellular carcinoma (HCC). In this study, we investigated the expression and possible role of miR-199a-5p in HCC. The expression of miR-199a-5p was measured by quantitative RT-PCR in HCC. The effect of miR-199a-5p was evaluated by cell viability and colony formation assays in HCC cell lines and tumor cell growth assay in xenograft nude mice. Quantitative real time PCR results showed that miR-199a-5p was down-regulated in 77.9 % (67/86) of HCC tissues compared with adjacent nontumor tissues. MiR-199a-5p mimic reduced cell viability and colony formation by induction of cell arrest in HCC cell lines and inhibited tumor cell growth in xenograft nude mice, but miR-199a-5p inhibitor increased cell viability and colony formation in HCC cell lines and tumor cell growth in xenograft nude mice. Furthermore, CLTC was defined as a potential direct target of miR-199a-5p by MiRanda and TargetScan predictions. The dual-luciferase reporter gene assay results showed that CLTC was a direct target of miR-199a-5p. The use of miR-199a-5p mimic or inhibitor could decrease or increase CLTC protein levels in HCC cell lines. We conclude that the frequently down-regulated miR-199a-5p can regulate CLTC and might function as a tumor suppressor in HCC. Therefore, miR-199a-5p may serve as a useful therapeutic agent for miRNA-based HCC therapy.
authors.affiliation: Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Guo-Hao
authors.initials: GH
authors.lastname: Huang
authors.affiliation: Department of Interventional Radiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.|Interventional Radiology Institute, Sun Yat-sen University, Zhuhai, China.
authors.forename: Hong
authors.identifier: http://orcid.org/0000-0002-8896-5813
authors.initials: H
authors.lastname: Shan
authors.affiliation: Department of Interventional Radiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Interventional Radiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.|Interventional Radiology Institute, Sun Yat-sen University, Zhuhai, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Interventional Radiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.|Interventional Radiology Institute, Sun Yat-sen University, Zhuhai, China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Pang
mesh_terms: D000368:Aged; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D033922:Clathrin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009368:Neoplasm Transplantation; D015398:Signal Transduction
chemical_list: C543704:CLTC protein, human; D035683:MicroRNAs; C531408:mirn199 microRNA, human; D033922:Clathrin Heavy Chains; D008156:Luciferases
keywords: CLTC; Hepatocellular carcinoma; cell growth; miR-199a-5p