Rho GTPase‐activating protein 1 promotes hepatocellular carcinoma progression via modulation by CircPIP5K1A/MiR‐101‐3p

Abstract

AimThere has been an increased focus on regulating cell function with Rho family GTPases, including proliferaton, migration/invasion, polarity and adhesion. Due to the challenges involved in targeting Rho family GTPases directly, it may be more effective to target their regulators, such as ARHGAP1. This present research was performed to define the clinical significance of ARHGAP1 expression as well as its regulatory mechanisms in hepatocellular carcinoma (HCC).MethodsARHGAP1 and miR‐101‐3p expression of liver cancer patients and their relevance with clinicopathological characteristics and prognosis were analyzed by the Cancer Genome Atlas sequencing data and verified using samples of HCC patients. The interactions between miR‐101‐3p and ARHGAP1 or circPIP5K1A were validated by bioinformatic analyses as well as confirmed by qRT‐PCR, western blotting and dual‐luciferase reporter analysis. Plate clonality assays, cell adhesion and migration experiments and proliferation experiments were used for assessing the participation of circPIP5K1A /miR‐101‐3p/ARHGAP1 pathway in cell proliferation and motility.ResultsElevated ARHGAP1 and reduced miR‐101‐3p expression are related to poorer survival. MiR‐101‐3p targets ARHGAP1 to suppress HCC cell colony formation and invasion, while miR‐101‐3p inhibitor reverses liver cancer proliferation and metastasis suppression caused by ARHGAP1 knockdown. In addition, circPIP5K1A, which is mainly distributed in the cytosol, showed carcinogenic effects by sponging miR‐101‐3p, thus regulating ARHGAP1 expression.ConclusionsARHGAP1 serves as an oncogenic gene in liver cancer and the expression thereof is regulated by CircPIP5K1A through sponging miR‐101‐3p.This article is protected by copyright. All rights reserved.