Ftx non coding RNA-derived miR-545 promotes cell proliferation by targeting RIG-I in hepatocellular carcinoma

Abstract

// Zhikui Liu 1, * , Changwei Dou 1, * , Bowen Yao 1 , Meng Xu 1 , Linglong Ding 1 , Yufeng Wang 1 , Yuli Jia 1 , Qing Li 1 , Hongyong Zhang 1 , Kangsheng Tu 1 , Tao Song 1 , Qingguang Liu 1 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China * These authors have contributed equally to this work Correspondence to: Qingguang Liu, email: liuqingguang@vip.sina.com Tao Song, email: 13572431619@163.com Kangsheng Tu, email: tks0912@foxmail.com Keywords: Ftx, miR-545, hepatocellular carcinoma, RIG-I, proliferation Received: January 25, 2016    Accepted: March 02, 2016    Published: March 16, 2016 ABSTRACT Hepatocellular carcinoma (HCC) is the third cause of cancer-related death worldwide. Accumulating studies have demonstrated that aberrant expression of several lncRNAs was found to be involved in the hepatocarcinogenesis. In this study, a lncRNA Ftx was chosen to investigate its effects on HCC cells, and clarify the possible mechanism. We demonstrated that the lncRNA Ftx and Ftx-derived miR-545 were up-regulated in both HCC tissues and cells. MiR-545 was positively correlated with lncRNA Ftx expression. Notably, clinical association analysis revealed that the high expression of lncRNA Ftx and miR-545 was associated with poor prognostic features, and conferred a reduced 5-year overall survival (OS) and disease-free survival (DFS) of HCC patients. We found that miR-545 was a pivotal mediator in Ftx-induced promotion of HCC cell growth. Subsequently, we identified RIG-I as a direct target of miR-545. The expression of RIG-I was downregulated in HCC tissues and was inversely correlated with miR-545 expression. Our data revealed that ectopic expression of RIG-I abrogated the effects of lncRNA Ftx or miR-545 on HCC cells. LncRNA Ftx/miR-545-mediated downregulation of RIG-I led to increased Akt phosphorylation in vitro and in vivo . Inhibition of Akt phosphorylation abolished the effects of lncRNA Ftx/miR-545 on HCC cells. In conclusion, our study demonstrates that the novel pathway lncRNA Ftx/miR-545/RIG-I promotes HCC development by activating PI3K/Akt signaling, and it may serve as a novel prognostic biomarker and therapeutic target for HCC.