title: MiR-148b suppresses cell proliferation and invasion in hepatocellular carcinoma by targeting WNT1/β-catenin pathway.
abstract: Accumulating evidences indicate that microRNAs play a vital role in regulating tumor progression. However, the roles of miR-148b in hepatocellular carcinoma (HCC) are still largely unknown. In this study, our data showed that miR-148b was significantly downregulated in 40 pairs of human HCC tissues. Further, the deregulated miR-148b was significantly correlated with larger tumor size, more tumor number, metastasis and worse prognosis in HCC. Overexpression of miR-148b inhibited HCC HepG2 cells proliferation and tumorigenicity. Further, miR-148b induced cells apoptosis by activating caspase- 3 and caspase-9, and induced S phase arrest by regulating cyclinD1 and p21, and also inhibited cell invasion. Data from the dual-luciferase reporter gene assay showed that WNT1 was a direct target of miR-148b, and overexpressed WNT1 inversely correlated with miR-148b levels in HCC tissues. Silencing of WNT1 inhibited the growth of HCC cells, and also induced cells apoptosis and inhibited invasion, which is consistent with the effects of miR-148b overexpression. MiR-148b downregulated expression of WNT1, β-catenin and C-myc, while upregulated E-cadherin expression. We conclude that the frequently downregulated miR-148b can regulate WNT1/β-catenin signalling pathway and function as a tumor suppressor in HCC. These findings suggest that miR-148b may serve as a novel therapeutic target for HCC.
authors: 1] Pancreatic Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China [2] Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou, 310014, China.
authors: Jun-gang
authors: JG
authors: Zhang
authors: Obstetrics and Gynecology, Zhejiang Provincial People's Hospital, Hangzhou, 310014, China.
authors: Ying
authors: Y
authors: Shi
authors: Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou, 310014, China.
authors: De-fei
authors: DF
authors: Hong
authors: Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors: Mengqi
authors: M
authors: Song
authors: Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou, 310014, China.
authors: Dongsheng
authors: D
authors: Huang
authors: Pancreatic Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors: Chun-you
authors: CY
authors: Wang
authors: Pancreatic Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors: Gang
authors: G
authors: Zhao
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D016019:Survival Analysis; D014162:Transfection; D060449:Wnt Signaling Pathway; D051155:Wnt1 Protein / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C550570:MIRN148 microRNA, human; D035683:MicroRNAs; D051155:Wnt1 Protein
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