Affiliation:
1. Department of Ultrasound Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou Guangdong Province China
2. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou Guangdong Province China
3. Department of Ultrasound West China Hospital Sichuan University Chengdu China
4. Laboratory of Ultrasound Medicine West China Hospital Sichuan University Chengdu China
Abstract
AbstractAimThere has been an increased focus on regulating cell function with Rho family GTPases, including proliferation, 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 Rho GTPase‐activating protein 1 (ARHGAP1). This present research was performed to define the clinical significance of ARHGAP1 expression, as well as its regulatory mechanisms in hepatocellular carcinoma.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 hepatocellular carcinoma patients. The interactions between miR‐101‐3p and ARHGAP1 or circPIP5K1A were validated by bioinformatic analyses, as well as confirmed by quantitative reverse transcription polymerase chain reaction, 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 the 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 hepatocellular carcinoma cell colony formation and invasion, whereas 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.
Funder
National Natural Science Foundation of China
Basic and Applied Basic Research Foundation of Guangdong Province
Subject
Infectious Diseases,Hepatology