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http://dx.doi.org/10.14348/molcells.2018.0181

MicroRNA-766-3p Inhibits Tumour Progression by Targeting Wnt3a in Hepatocellular Carcinoma  

You, Yu (Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University)
Que, Keting (Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University)
Zhou, Yun (Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University)
Zhang, Zhen (Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University)
Zhao, Xiaoping (Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University)
Gong, Jianpin (Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University)
Liu, Zuojin (Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University)
Publication Information
Molecules and Cells / v.41, no.9, 2018 , pp. 830-841 More about this Journal
Abstract
Recent studies have indicated that microRNAs (miRNAs) play an important role in hepatocellular carcinoma (HCC) progression. In this study, we showed that miR-766-3p was decreased in approximately 72% of HCC tissues and cell lines, and its low expression level was significantly correlated with tumour size, TNM stage, metastasis, and poor prognosis in HCC. Ectopic miR-766-3p expression inhibited HCC cell proliferation, colony formation, migration and invasion. In addition, we showed that miR-766-3p repressed Wnt3a expression. A luciferase reporter assay revealed that Wnt3a was a direct target of miR-766-3p, and an inverse correlation between miR-766-3p and Wnt3a expression was observed. Moreover, Wnt3a up-regulation reversed the effects of miR766-3p on HCC progression. In addition, our study showed that miR-766-3p up-regulation decreased the nuclear ${\beta}-catenin$ level and expression of Wnt targets (TCF1 and Survivin) and reduced the level of MAP protein regulator of cytokinesis 1 (PRC1). However, these effects of miR-766-3p were reversed by Wnt3a up-regulation. In addition, PRC1 upregulation increased the nuclear ${\beta}-catenin$ level and protein expression of TCF1 and Survivin. iCRT3, which disrupts the ${\beta}-catenin-TCF4$ interaction, repressed the TCF1, Survivin and PRC1 protein levels. Taken together, our results suggest that miR-766-3p down-regulation promotes HCC cell progression, probably by targeting the Wnt3a/PRC1 pathway, and miR-766-3p may serve as a potential therapeutic target in HCC.
Keywords
hepatocellular carcinoma; invasion; miR-766-3p; proliferation; Wnt3a;
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