Abstract 3081: miR-885-5p, a p53-activated microRNA, inhibits the Wnt/β-catenin signaling pathway and hepatocellular carcinoma metastasis.

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.