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

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...

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Bibliographic Details
Published in:Oncotarget 2016-05, Vol.7 (18), p.25350-25365
Main Authors: Liu, Zhikui, Dou, Changwei, Yao, Bowen, Xu, Meng, Ding, Linglong, Wang, Yufeng, Jia, Yuli, Li, Qing, Zhang, Hongyong, Tu, Kangsheng, Song, Tao, Liu, Qingguang
Format: Article
Language:English
Subjects:
Adult
Aged
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - mortality
Carcinoma, Hepatocellular - pathology
Cell Proliferation - genetics
Disease-Free Survival
Female
Gene Expression Regulation, Neoplastic - genetics
Humans
Kaplan-Meier Estimate
Liver Neoplasms - genetics
Liver Neoplasms - mortality
Liver Neoplasms - pathology
Male
MicroRNAs - genetics
Middle Aged
Receptors, Retinoic Acid - biosynthesis
Receptors, Retinoic Acid - genetics
Research Paper
RNA, Long Noncoding - genetics
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Summary: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.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.8129