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Updated: Jul 15, 2025

In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines
Published on: April 18, 2025
Rho GTPase-activating protein 1 promotes hepatocellular carcinoma progression via modulation by
Yanni Xu1,2, Xiaodi Liu3,4, Jincheng Cao1,2
1Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
Aim:
There 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.
Methods:
ARHGAP1 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.
Results:
Elevated 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.
Conclusions:
ARHGAP1 serves as an oncogenic gene in liver cancer, and the expression thereof is regulated by circPIP5K1A through sponging miR-101-3p.
Insights
Rho GTPase-activating protein 1 (ARHGAP1) acts as an oncogene in liver cancer, promoting proliferation and metastasis. Its expression is regulated by circPIP5K1A via sponging miR-101-3p, offering potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Rho family GTPases regulate critical cell functions, including proliferation and migration.
- Targeting Rho GTPase regulators like ARHGAP1 is a strategy for hepatocellular carcinoma (HCC) treatment.
- Understanding ARHGAP1's clinical significance and regulatory mechanisms in HCC is crucial.
Purpose of the Study:
- To define the clinical significance of ARHGAP1 expression in HCC.
- To elucidate the regulatory mechanisms of ARHGAP1 in HCC.
- To investigate the role of the circPIP5K1A/miR-101-3p/ARHGAP1 pathway in HCC progression.
Main Methods:
- Analysis of ARHGAP1 and miR-101-3p expression in HCC patient data (TCGA).
- Validation using HCC patient samples and molecular biology techniques (qPCR, Western blotting, dual-luciferase reporter assays).
- Functional assays (clonality, adhesion, migration, proliferation) to assess pathway involvement.
Main Results:
- Elevated ARHGAP1 and reduced miR-101-3p correlate with poorer HCC patient survival.
- MiR-101-3p suppresses HCC cell growth and invasion by targeting ARHGAP1.
- circPIP5K1A acts as a carcinogenic sponge for miR-101-3p, upregulating ARHGAP1 expression.
Conclusions:
- ARHGAP1 functions as an oncogene in liver cancer.
- circPIP5K1A promotes HCC by sponging miR-101-3p, thereby regulating ARHGAP1.
- The circPIP5K1A/miR-101-3p/ARHGAP1 axis represents a novel regulatory pathway in HCC.
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