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.
Highlights
Hepatocellular carcinoma (HCC) is the most common primary malignancy in liver and the third leading cause of cancer-related death worldwide [1]
The results showed that the expression of long non-coding RNAs (lncRNAs) Ftx and miR-545 in HCC tissues were significantly higher than that in the non-tumor tissues (P
Further results confirmed that lncRNA Ftx and miR-545 were upregulated in a panel of HCC cell lines (HepG2, Huh7, Hep3B, SMMC-7721 and Bel-7402) compared with that in non-transformed LO2 hepatic cell line (P
Summary
Hepatocellular carcinoma (HCC) is the most common primary malignancy in liver and the third leading cause of cancer-related death worldwide [1]. Aberrant expression of several lncRNAs play crucial roles in various physiological and pathological processes, such as cell proliferation, apoptosis, differentiation, migration and invasion [9]. These lncRNAs www.impactjournals.com/oncotarget could be employed as novel therapeutic targets [10]. Previous studies show that miR-545 functions as a regulator of cell proliferation, cell cycle and apoptosis in human cancers [17]. MiR-545 enhanced radiosensitivity via suppressing Ku70 expression and tumor-specific recruitment of regulator T cells in lung carcinoma [18, 19]. The expression of miR-545 and its role in HCC initiation and progression, and whether it can exert its function by targeting RIG-I in HCC remain unknown. The clinical significance of lncRNA Ftx and its biological functions, and co-expression network of lncRNA Ftx and miR-545 are poorly investigated
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
