Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2025; 31(2): 100898
Published online Jan 14, 2025. doi: 10.3748/wjg.v31.i2.100898
RGS4 promotes the progression of gastric cancer through the focal adhesion kinase/phosphatidyl-inositol-3-kinase/protein kinase B pathway and epithelial-mesenchymal transition
Peng-Yu Chen, Pei-Yao Wang, Bang Liu, Yang-Pu Jia, Zhao-Xiong Zhang, Xin Liu, Dao-Han Wang, Yong-Jia Yan, Wei-Hua Fu, Feng Zhu
Peng-Yu Chen, Pei-Yao Wang, Bang Liu, Yang-Pu Jia, Zhao-Xiong Zhang, Xin Liu, Dao-Han Wang, Yong-Jia Yan, Wei-Hua Fu, Feng Zhu, Department of General Surgery, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin 300052, China
Feng Zhu, Department of General Surgery, Jincheng People’s Hospital, Jincheng 048000, Shanxi Province, China
Co-first authors: Peng-Yu Chen and Pei-Yao Wang.
Co-corresponding authors: Wei-Hua Fu and Feng Zhu.
Author contributions: Fu WH and Zhu F designed the research study and contributed new reagents and analytic tools, they are the corresponding authors of this manuscript; Chen PY, Wang PY, Liu B, Jia YP, Zhang ZX, Liu X, Wang DH, Yan YJ, and Zhu F performed the research; Chen PY and Wang PY analyzed the date and wrote the manuscript, they are the co-first authors of this manuscript; and all authors have read and approved the final manuscript.
Supported by the Fundamental Research Program of Shanxi Province, No. 202203021222418; Research Program of Shanxi Provincial Health Commission, No. 2023061; Fundamental Research Cooperation Program of Beijing-Tianjin-Hebei Region of Natural Science Foundation of Tianjin, No. 22JCZXJC00140; Tianjin Major Science and Technology Project, No. 21ZXJBSY00110; and Tianjin Health and Science and Technology Project, No. TJWJ2024ZK001.
Institutional review board statement: The study was reviewed and approved by the Ethical Committee of Tianjin Medical University General Hospital, No. IRB2024-YX-413-01.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Tianjin Medical University General Hospital, No. IRB2024-DW-81.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at tjmughgs_fwh@163.com.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wei-Hua Fu, MD, PhD, Professor, Surgeon, Department of General Surgery, Tianjin Medical University General Hospital, Tianjin Medical University, No. 154 Anshan Road, Tianjin 300052, China. tjmughgs_fwh@163.com
Received: August 29, 2024
Revised: September 28, 2024
Accepted: November 20, 2024
Published online: January 14, 2025
Processing time: 110 Days and 19.1 Hours
Abstract
BACKGROUND

Regulator of G protein signaling (RGS) proteins participate in tumor formation and metastasis by acting on the α-subunit of heterotrimeric G proteins. The specific effect of RGS, particularly RGS4, on the progression of gastric cancer (GC) is not yet clear.

AIM

To explore the role and underlying mechanisms of action of RGS4 in GC development.

METHODS

The prognostic significance of RGS4 in GC was analyzed using bioinformatics based public databases and verified by immunohistochemistry and quantitative polymerase chain reaction in 90 patients with GC. Function assays were employed to assess the carcinogenic impact of RGS4, and the mechanism of its possible influence was detected by western blot analysis. A nude mouse xenograft model was established to study the effects of RGS4 on GC growth in vitro.

RESULTS

RGS4 was highly expressed in GC tissues compared with matched adjacent normal tissues. Elevated RGS4 expression was correlated with increased tumor-node-metastasis stage, increased tumor grade as well as poorer overall survival in patients with GC. Cell experiments demonstrated that RGS4 knockdown suppressed GC cell proliferation, migration and invasion. Similarly, xenograft experiments confirmed that RGS4 silencing significantly inhibited tumor growth. Moreover, RGS4 knockdown resulted in reduced phosphorylation levels of focal adhesion kinase, phosphatidyl-inositol-3-kinase, and protein kinase B, decreased vimentin and N-cadherin, and elevated E-cadherin.

CONCLUSION

High RGS4 expression in GC indicates a worse prognosis and RGS4 is a prognostic marker. RGS4 influences tumor progression via the focal adhesion kinase/phosphatidyl-inositol-3-kinase/protein kinase B pathway and epithelial-mesenchymal transition.

Keywords: Gastric cancer; Prognosis; Regulator of G protein signaling 4; Focal adhesion kinase; Epithelial-mesenchymal transition

Core Tip: This study explored the relevant role of regulator of G protein signaling 4 (RGS4) in gastric cancer (GC) and its possible mechanism. Through analysis of public databases, validation of clinical specimens, cell experiments and xenograft model, our study confirmed that RGS4 promotes GC progression through the focal adhesion kinase/phosphatidyl-inositol-3-kinase/protein kinase B pathway and epithelial-mesenchymal transition. RGS4 is a potential therapeutic target for GC and our study may further guide clinical practice.