title: miR-365 targets ADAM10 and suppresses the cell growth and metastasis of hepatocellular carcinoma.
abstract: Expression of miR-365 has been reported to be downregulated in hepatocellular carcinoma (HCC). However, the biological function and underlying mechanism of miR-365 in HCC growth and metastasis remain unclear. The aim of the present study was to explore the role of miR-365 in HCC progression. We found that miR-365 expression was downregulated in HCC tissues and cell lines. Further results showed that low expression of miR-365 was significantly associated with tumor-node-metastasis (TNM) stage and lymph node metastasis. Functional assays revealed that overexpression of miR-365 significantly inhibited cell proliferation, colony formation, migration and invasion of HCC cells in vitro, and suppressed tumor growth in vivo. Mechanistic investigations demonstrated that ADAM10 (a disintegrin and metalloproteinase 10) is a target of miR-365 in HCC. In addition, knockdown of ADAM10 in HepG2 cells significantly inhibited cell proliferation, colony formation, migration and invasion, which mimicked the suppressive effects induced by miR-365 overexpression. Restoration of ADAM10 expression partially reversed the suppressive effects mediated by miR-365 overexpression. Taken together, these results indicate that miR-365 functions as a tumor-suppressor in HCC through targeting ADAM10, and may serve as a promising candidate for therapeutic applications in HCC treatment.
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Songyang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Bai
authors.initials: B
authors.lastname: Ji
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Yingchao
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000072197:ADAM10 Protein / Q000235:genetics / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: C546819:MIRN365 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D053829:Amyloid Precursor Protein Secretases; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human