LncRNA RMRP/miR-613 axis is associated with poor prognosis and enhances the tumorigenesis of hepatocellular carcinoma by impacting oncogenic phenotypes.

Increasing evidences demonstrate that long noncoding RNAs (lncRNAs) play an important role in the tumorigenesis of hepatocellular carcinoma (HCC). LncRNA RMRP (RNA component of mitochondrial RNA processing endoribonuclease) has been proved to involve in the tumorigenesis of several human cancers. However, the role and molecular mechanism of RMRP in HCC remain largely unknown. In current study, we compared the expression profiles of RMRP in 52 paired HCC specimens and corresponding adjacent non-tumor tissues. The clinicopathological characteristics of HCC patients in relation to RMRP expression were analyzed, and the prognostic value of RMRP expression was examined. RNAi technology was performed to knockdown RMRP expression in HCC cells, and the effects of RMRP on cell proliferation, cell cycle, migration and invasion of HCC cells were assessed by using MTT, flow cytometry, wound scratch and transwell invasion assays. The potential binding site of RMRP to miR-613 was confirmed by using dual luciferase reporter gene and qRT-PCR assays. Here, we found that RMRP expression was significantly upregulated in the HCC tissues and cells, and high RMRP expression was positively correlated with tumor aggressive phenotypes and poor overall survival of patients with HCC. Furthermore, RMRP knockdown suppressed cell proliferation, migration, invasion and induced cell cycle arrest at G0/G1 phase. The expression of miR-613 was dramatically down-regulated in HCC tissues and cells, and RMRP could negatively regulate miR-613 expression by acting as a ceRNA. In mechanism, RMRP exerted an oncogenic role in HCC via downregulation of miR-613. In vivo experiment also revealed that RMRP knockdown inhibited HCC tumorigenesis, while miR-613 silencing could partly reversed the inhibitory effect of RMRP knockdown on HCC tumorigenesis. In conclusion, our data demonstrated that RMRP plays an oncogenic role in regulating HCC tumorigenesis by acting as a ceRNA of miR-613, indicating RMRP/miR-613 axis may serve as a novel molecular target for the treatment of HCC.