1. MiR-148b suppresses cell proliferation and invasion in hepatocellular carcinoma by targeting WNT1/β-catenin pathway.
- Author
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Zhang JG, Shi Y, Hong DF, Song M, Huang D, Wang CY, and Zhao G
- Subjects
- 3' Untranslated Regions genetics, Aged, Animals, Apoptosis genetics, Base Sequence, Blotting, Western, Cell Cycle Checkpoints genetics, Cell Proliferation, Female, Gene Expression Regulation, Neoplastic, Hep G2 Cells, Humans, Liver metabolism, Liver pathology, Male, Mice, Inbred BALB C, Mice, Nude, MicroRNAs genetics, Middle Aged, Molecular Sequence Data, Neoplasm Invasiveness, Survival Analysis, Transfection, Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular pathology, Liver Neoplasms genetics, Liver Neoplasms pathology, MicroRNAs metabolism, Wnt Signaling Pathway, Wnt1 Protein metabolism
- 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.
- Published
- 2015
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