Title:RHPN1-AS1 Drives the Progression of Hepatocellular Carcinoma via Regulating miR-596/IGF2BP2 Axis
Volume: 25
Issue: 43
Author(s): Hu Fen, Zheng Hongmin, Wei Wei, Yang Chao, Yao Yang, Liu Bei and Sun Zhihua*
Affiliation:
- Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441000, Hubei,China
Keywords:
RHPN1-AS1, miR-596, IGF2BP2, HCC, oncogenic lncRNA, CCK-8.
Abstract: 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.
Methods: 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.
Results: 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.