title: MicroRNA-133a functions as a tumor suppressor by targeting IGF-1R in hepatocellular carcinoma.
abstract: MicroRNAs (miRNAs) are a class of small non-coding RNAs and have critical roles in tumorigenesis and metastasis. A growing body of evidence showed that microRNA-133a (miR-133a) was downregulated and played tumor suppressor roles in gastric, colorectal, bladder, and lung cancer. However, the role and underlying molecular mechanism of miR-133a in hepatocellular carcinoma (HCC) remain unclear. In this study, we analyzed the expression of miR-133a in HCC tissues and HCC cell lines. We find that miR-133a was downregulated in HCC tissues and cell lines and that miR-133a expression negatively correlated with tumor differentiation (P < 0.01), TNM stage (P < 0.01), and lymph node metastasis (P < 0.01). Then, functional studies demonstrate that restoration of miR-133a in HepG2 cells significantly suppressed proliferation, colony formation, migration, and invasion, induced cell cycle arrest at G0/G1 stage and cell apoptosis in vitro, and decreased tumor size and weight in a nude mouse HepG2 xenograft model. Using bioinformatics method and dual luciferase assays identified insulin-like growth factor 1 receptor (IGF-1R) as a direct target of miR-133a in HCC cells. Furthermore, overexpression of miR-133a inhibited activation AKT and ERK signal pathway, which contributed to suppression of HCC cell growth. These findings suggest that miR-133a may act as a tumor suppressor and inhibited survival of HCC cells by targeting IGF-1R.
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, the First Hospital of Jilin University, Changchun, 130021, Jilin Province, China. zhangwei1424@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, the First Hospital of Jilin University, Changchun, 130021, Jilin Province, 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, 130021, Jilin Province, 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, 130021, Jilin Province, 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, 130021, Jilin Province, China.
authors.forename: Yingchao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, the First Hospital of Jilin University, Changchun, 130021, Jilin Province, China. liuyahui588@126.com.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays
chemical_list: C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D017526:Receptor, IGF Type 1
keywords: Hepatocellular carcinoma; IGF-1R; MicroRNAs; miR-133a