title: miR-613 inhibits the growth and invasiveness of human hepatocellular carcinoma via targeting DCLK1.
abstract: microRNAs (miRNAs) play key regulatory roles in various biological processes. In this study, we aimed to determine the expression and biological roles of miR-613 in hepatocellular carcinoma (HCC). Compared with non-cancerous liver tissues, miR-613 was significantly downregulated in HCC tissues. Ectopic expression of miR-613 significantly suppressed the proliferation and invasion of Hep3B and SMMC-7721 HCC cells. Bioinformatic and luciferase reporter analysis identified doublecortin-like kinase 1 (DCLK1) as a direct target of miR-613. Overexpression of miR-613 inhibited the expression of DCLK1 in HCC cells. There was a significant inverse correlation between miR-613 and DCLK1 protein expression in HCC samples. Small interfering RNA-mediated silencing of DCLK1 phenocopied the suppressive effects of miR-613 in HCC cells. Rescue experiments demonstrated that co-transfection of DCLK1 lacking the 3'-untranslated region partially prevented miR-613-induced suppression of HCC cell proliferation and invasion. In vivo studies confirmed that miR-613 overexpression retarded the growth of Hep3B xenograft tumors in nude mice, coupled with a reduction in the percentage of Ki67-positive tumor cells and DCLK1 protein expression. In conclusion, we provide first evidence for the suppressive activity of miR-613 in HCC, which is causally linked to targeting of DCLK1. Restoration of miR-613 may provide a potential therapeutic strategy for HCC.
authors.affiliation: Department of General Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China. Electronic address: wangwy117@163.com.
authors.forename: Wenyao
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Lichao
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Shaojun
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Tang
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000089742:Doublecortin-Like Kinases; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C561374:MIRN613 microRNA, human; D035683:MicroRNAs; C117347:DCLK1 protein, human; D000089742:Doublecortin-Like Kinases; D017346:Protein Serine-Threonine Kinases
keywords: Dysregulation; Growth; Invasiveness; Target; microRNA