Abstract
Abstract The regulation of hepatocelluar carcinoma (HCC) progression by microRNAs (miRNAs) has attracted attention in recent years. Our previous study reported that the levels of circulating miR-885-5p were significantly up-regulated in patients with HCC and chronic hepatitis B (CHB). However, the role of miR-885-5p in HCC metastasis and the underlying mechanisms remain unknown. In this study, we used in situ hybridization to analyze the expression of miR-885-5p in HCC tissues and found that its expression was negatively associated with TNM stage of HCC. Consistent with this, the expression of miR-885-5p was negatively correlated with the invasive and metastatic abilities of human HCC cell lines. Kaplan-Meier analysis revealed that miR-885-5p levels correlated with the survival of HCC patients. Furthermore, enforced expression of miR-885-5p in high-metastatic HCC cells inhibited migration and invasion in vitro and in vivo. In addition, we identified that miR-885-5p directly targeted genes encoding the β-catenin CTNNB1 and the transcription factor TCF4, leading to decreased activity of the Wnt/β-catenin signaling pathway, which in turn contributes to metastasis in various cancers, including HCC. Notably, our results also showed that p53 up-regulated the expression of miR-885-5p and significantly inactivated the Wnt/β-catenin signaling pathway in HCC cells. We found that miR-885-5p levels correlated with wild-type TP53 status in HCC tissues. Taken together, these findings suggest that miR-885-5p is a negative regulator of HCC metastasis and indicate a potent rationale for developing miR-885-5p as a potential therapeutic agent against HCC metastasis. Citation Format: Zhuhong Zhang, Jing Yin, Dan Lv, Chenghu Liu, Jian Yang, Antao Chang, Peiqing Sun, Si Chen, Dwayne Stupack, Yaping Tian, Rong Xiang. miR-885-5p, a p53-activated microRNA, inhibits the Wnt/β-catenin signaling pathway and hepatocellular carcinoma metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3081. doi:10.1158/1538-7445.AM2013-3081 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
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