Previous studies have indicated that Zinc ribbon domain-containing 1 (ZNRD1) is attributed to the carcinogenesis of human tumors. However, the role of ZNRD1 and its regulation in hepatocellular carcinoma (HCC) are still largely unclear. In this study, we examined the expression profiles of ZNRD1 in HCC tissues by immunohistochemistry (IHC) and publicly datasets analysis. In vitro and in vivo experiments were conducted to identify the function of ZNRD1 in HCC. In addition, miRNA potentially targeting ZNRD1 was predicted by bioinformatics analysis and further verified via in vitro experiments. Our results revealed that ZNRD1 was frequently upregulated in HCC tissues compared with that in nontumor tissues. High ZNRD1 expression in HCC tissues was positively associated with advanced tumor stage and poor prognosis. Function experiments showed that knockdown of ZNRD1 inhibited cell growth and invasion in vitro, and suppressed tumor development in vivo. Moreover, ZNRD1 promoted the activation of Wnt/β-catenin signaling pathway in HCC. Importantly, miR-26b directly inhibited the transcription activity of ZNRD1. Overexpression of ZNRD1 dramatically abolished the inhibitory effects of miR-26b on HCC cells. Taken together, our results uncover a novel mechanistic role for miR-26b/ZNRD1 axis in HCC, proposing ZNRD1 inhibition as a potent therapeutic strategy for hepatocellular carcinoma.
Keywords: HCC; Wnt/β-catenin signaling pathway; ZNRD1; miR-26b.
© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.