RHPN1-AS1 Drives the Progression of Hepatocellular Carcinoma via Regulating miR-596/IGF2BP2 Axis

Background: Hepatocellular carcinoma (HCC) is one of the most deadly cancer types worldwide, and its incidence is high in China. Multiple long non-coding RNAs (lncRNAs) have been recently identified as crucial oncogenic factors or tumor suppressors. In this study, we explored the effects of LncRNA RHPN1 antisense RNA 1 (RHPN1-AS1) on the progression of HCC. Method: Expression levels of RHPN1-AS1 and miR-596 in HCC samples were measured by qRT-PCR. The association between pathological indexes and the expression level of RHPN1-AS1 was also analyzed. Human HCC cell lines Huh7 and SMMC-7721 were used as cell models. CCK-8 and colony formation assays were performed to assess the effect of RHPN1-AS1 on HCC cell line proliferation. The flow cytometer instrument was used to study the effect of RHPN1-AS1 on apoptosis of HCC cells. The transwell assay was conducted to detect the effect of RHPN1-AS1 on migration and invasion. Furthermore, luciferase reporter assay was used to confirm targeting of miR-596 by RHPN1-AS1. Additionally, the regulatory function of RHPN1-AS1 on insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) was detected by western blot. Result: The expression level of RHPN1-AS1 in HCC samples was observed to significantly increase compared with normal tissues and its high expression was correlated with unfavorable pathological indexes. Highly expressed RHPN1-AS1 was associated with shorter overall survival time. RHPN1-AS1 overexpression remarkably accelerated proliferation and metastasis of HCC cells, while reduced apoptosis. Accordingly, RHPN1-AS1 knockdown suppressed the malignant phenotypes of HCC cells. RHPN1-AS1 overexpression significantly reduced miR-596 expression by sponging it, but enhanced IGF2BP2 expression. Conclusion: RHPN1-AS1 acts as a sponge of tumor suppressor miR-596 in HCC that can indirectly enhance the IGF2BP2 expression and function as an oncogenic lncRNA.