Long Noncoding RNA RP5-833A20.1 Suppresses Tumorigenesis In Hepatocellular Carcinoma Through Akt/ERK Pathway By Targeting miR-18a-5p.

ABSTRACT

BACKGROUND: Previous studies indicated that long noncoding RNAs (lncRNAs) played vital roles in the development and progression of hepatocellular carcinoma (HCC). Recently, downregulation of lncRNA RP5­833A20.1 has been observed in HCC tissues. However, the underlying mechanism by which RP5­833A20.1 regulates the proliferation and apoptosis in HCC has not been investigated. Thus, this study aimed to investigate the role of RP5­833A20.1 in the progression of HCC. METHODS: The levels of RP5­833A20.1 in 30 pairs of HCC tissues and adjacent normal tissues were detected by RT-qPCR. In addition, the effects of RP5­833A20.1 on cell proliferation, apoptosis and invasion were evaluated by CCK-8, flow cytometric, transwell assays, respectively. Meanwhile, the dual-luciferase reporter system assay was used to explore the interaction of RP5­833A20.1 and miR-18a-5p in HCC. RESULTS: The level of RP5­833A20.1 was significantly downregulated in HCC tissues and HCC cell lines. Downregulation of RP5­833A20.1 markedly promoted the proliferation and invasion of Bel-7402 cells. In addition, overexpression of RP5­833A20.1 notably inhibited the proliferation and invasion of Huh7 cells. Moreover, overexpression of RP5­833A20.1 obviously induced the apoptosis of Huh7 cells via increasing the levels of Bax and active caspase 3, and decreasing the levels of Bcl-2, p-Akt and p-ERK. Meanwhile, in vivo experiments performed also indicated that overexpression of RP5-833A20.1 could inhibit the tumorigenesis of subcutaneous Huh7 xenograft in nude mice. Furthermore, bioinformatics and luciferase reporter assay identified that RP5-833A20.1 functioned as a competing endogenous RNA (ceRNA) for miR-18a-5p in HCC. CONCLUSION: In this study, we found that RP5­833A20.1 was downregulated in HCC tissues. In addition, RP5-833A20.1 could suppress the tumorigenesis in HCC through inhibiting Akt/ERK pathway by acting as a ceRNA for miR-18a-5p. Therefore, RP5-833A20.1 might be a valuable and potential biomarker and therapeutic target for the treatment of HCC.