microRNA-485-5p inhibits the progression of hepatocellular carcinoma through blocking the WBP2/Wnt signaling pathway.
microRNA-485-5p (miR-485-5p) has been shown to act as a tumor-suppressor gene in some cancers, such as ovarian epithelial tumors and oral tongue squamous cell carcinoma. However, with regard to the anti-tumor role of miR-485-5p in hepatocellular carcinoma (HCC), evidence is unexpectedly limited. In the present study, we investigated the expression and the role of miR-485-5p in the progression of HCC. Microarray analysis revealed that miR-485-5p was downregulated and WBP2 was upregulated in HCC, which was consistent with RT-qPCR and immunohistochemistry assays in the HCC tissues we collected. A negative correlation between the expression of miR-485-5p and WBP2 was also found in HCC tissues. It was predicted and confirmed that miR-485-5p could bind to WW domain binding protein 2 (WBP2) through in silico analysis of genetic sequences and an in vitro dual-luciferase reporter gene assay. Next, gain- or loss-of-function studies were applied in the HCC cell line (Huh7) to examine the effects of miR-485-5p and WBP2 on HCC cell behavior. The effects of miR-485-5p and WBP2 on the Wnt/β-catenin signaling pathway were determined by TOP/FOP flash luciferase assays. miR-485-5p was shown to downregulate WBP2 and block the Wnt/β-catenin signaling pathway. As expected, elevated miR-485-5p levels and inhibition of WBP2 protein expression exerted inhibitory effects on HCC cell proliferation, migration and invasion and, induced apoptosis. In vivo experiments were finally conducted, which confirmed that upregulation of miR-485-5p or depletion of WBP2 attenuated tumor growth. Collectively, our results suggest miR-485-5p can downregulate WBP2 to inhibit the development of HCC by the blockade of the Wnt/β-catenin signaling, providing a novel molecular target for HCC treatment.
['Gao|Jun|J|', 'Dai|Chao|C|', 'Yu|Xin|X|', 'Yin|Xiang-Bao|XB|', 'Zhou|Fan|F|']
D000328:Adult D000818:Animals D017209:Apoptosis D006528:Carcinoma, Hepatocellular D045744:Cell Line, Tumor D002465:Cell Movement D049109:Cell Proliferation D005260:Female D015972:Gene Expression Regulation, Neoplastic D006801:Humans D008113:Liver Neoplasms D008297:Male D051379:Mice D008807:Mice, Inbred BALB C D008819:Mice, Nude D035683:MicroRNAs D008875:Middle Aged D015534:Trans-Activators D060449:Wnt Signaling Pathway
microRNA-485-5p Hepatocellular carcinoma WW domain binding protein 2 Wnt/β-catenin signaling