title: MiR-132 inhibits cell proliferation, invasion and migration of hepatocellular carcinoma by targeting PIK3R3.
abstract: MicroRNA-132 (miR‑132) has been reported to play a tumor suppressive role in different human malignancies. However, its role and underling mechanism in hepatocellular carcinoma (HCC) remains poorly defined due to lack of target gene information. In the present study, we demonstrated that the mean level of miR‑132 in hepatocellular carcinoma (HCC) tissues was significantly lower than that in matched tumor-adjacent tissues, and its expression negatively correlated with tumor differentiation (P<0.01), TNM stage (P<0.01) and lymph node metastasis (P<0.01). Similarly, the expression of miR‑132 was obviously reduced in HCC cell lines as compared with a normal hepatic cell line. Ectopic expression of miR‑132 inhibited cell proliferation, colony formation, migration and invasion, and induced apoptosis in HepG2 cells. In vivo studies showed that miR‑132 inhibited tumor growth of HCC and decreased tumor volume and weight. In addition, phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) was identified as a direct target of miR‑132 by a luciferase reporter assay. Western blot and qRT-PCR analysis indicated that PIK3R3 was significantly downregulated by miR‑132 in HCC cells. miR‑132 expression inversely correlated with PIK3R3 mRNA expression in clinical HCC tissues. Investigations into possible mechanisms revealed that miR‑132 inactivated the AKT/mTOR signaling pathway, which may contribute to inhibition of proliferation, migration, and invasion of HCC. These findings suggested that miR‑132 may serve as a potential target in the treatment of human HCC.
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The First Hospital, Jilin University, Changchun 130021, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine Emergency, The First Hospital, Jilin University, Changchun 130021, P.R. China.
authors.forename: Xingliang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Clinical Medicine, Bethune Medical School, Jilin University, Changchun 130021, P.R. China.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Geriatrics, The First Hospital, Jilin University, Changchun 130021, P.R. China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ge
authors.affiliation: Department of Geriatrics, The First Hospital, Jilin University, Changchun 130021, P.R. China.
authors.forename: Jianmeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: The Experiment Center, School of Basic Medical Sciences, Jilin University, Changchun 130021, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Shi
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016147:Genes, Tumor Suppressor / Q000502:physiology; D056945:Hep G2 Cells; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis* / Q000235:genetics; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: C547077:MIRN132 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D019869:Phosphatidylinositol 3-Kinases; C523442:PIK3R3 protein, human