Gao Z, Zhang X, He H. Role and mechanism of sarcosine dehydrogenase in the progression of gallbladder cancer through chemokine pathways. World J Gastrointest Oncol 2025; 17(6): 105016 [DOI: 10.4251/wjgo.v17.i6.105016]
Corresponding Author of This Article
Hua He, Department of General Surgery, Qingpu Branch of Zhongshan Hospital, Fudan University, No. 1158 Park Road East, Qingpu District, Shanghai 201700, China. hehua-sh@21cn.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Oncol. Jun 15, 2025; 17(6): 105016 Published online Jun 15, 2025. doi: 10.4251/wjgo.v17.i6.105016
Role and mechanism of sarcosine dehydrogenase in the progression of gallbladder cancer through chemokine pathways
Zhen Gao, Xin Zhang, Hua He
Zhen Gao, Hua He, Department of General Surgery, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 201700, China
Xin Zhang, Department of Hepatobiliary Surgery, Pudong Hospital, Fudan University, Shanghai 200433, China
Co-first authors: Zhen Gao and Xin Zhang.
Author contributions: Gao Z and Zhang X contributed equally to this work; Gao Z designed the study, collected data, and drafted the manuscript; Zhang X conducted data analysis, performed statistical interpretation, and assisted with manuscript revisions; He H supervised the study, provided critical guidance, and contributed to the final manuscript editing; All authors have reviewed and approved the final version.
Supported by the Qingpu Science and Technology Commission Project, No. QKY2022-13.
Institutional review board statement: This study was conducted solely on commercially available cell lines and did not involve human participants, identifiable personal data, or the use of experimental animals. Therefore, the research was exempt from institutional review board approval.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: All data generated or analyzed during this study are included in this published article. Further details can be provided upon reasonable request from the corresponding author at hehua-sh@21cn.com.
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: Hua He, Department of General Surgery, Qingpu Branch of Zhongshan Hospital, Fudan University, No. 1158 Park Road East, Qingpu District, Shanghai 201700, China. hehua-sh@21cn.com
Received: February 7, 2025 Revised: March 10, 2025 Accepted: April 24, 2025 Published online: June 15, 2025 Processing time: 125 Days and 21.2 Hours
Abstract
BACKGROUND
Sarcosine dehydrogenase (SARDH) and C-X-C motif chemokine ligand 1 (CXCL1) have been identified as potential tumor regulators, with growing evidence linking them to cancer progression. However, their specific roles, regulatory mechanisms, and influence on key signaling pathways remain unclear.
AIM
To investigate the regulatory mechanisms of SARDH and CXCL1 in cancer cells and their impact on key signaling pathways.
METHODS
Real-time quantitative polymerase chain reaction and western blot analyses were used to assess the expression levels of SARDH and CXCL1 and their effects on protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) signaling pathways. Gene overexpression was induced using an expression vector, while gene silencing was achieved using short hairpin RNA and small interfering RNA. CCK-8, migration, and invasion assays were used to evaluate the impact of gene suppression and overexpression on cancer cell proliferation, migration, and invasion.
RESULTS
SARDH silencing significantly enhanced cancer cell proliferation, whereas its overexpression suppressed proliferation in the early stages of the experiment. CXCL1 silencing reduced cancer cell migration and invasion. SARDH overexpression inhibited cell migration, invasion, and adhesion while increasing apoptosis. Conversely, SARDH silencing reversed these effects. Furthermore, simultaneous silencing of SARDH and CXCL1 strongly activated the Akt and ERK signaling pathways, indicating the potential role of these pathways in regulating cellular functions influenced by these genes.
CONCLUSION
This study revealed that SARDH and CXCL1 regulate cancer cell growth, migration, and invasion through Akt and ERK signaling pathways, highlighting their potential as therapeutic targets for cancer treatment.
Core Tip: In this study, we examined the roles of sarcosine dehydrogenase (SARDH) and C-X-C motif chemokine ligand 1 (CXCL1) in cancer cells and their effects on key signaling pathways. SARDH silencing enhanced cell proliferation, whereas CXCL1 silencing suppressed migration and invasion, triggering protein kinase B and extracellular signal-regulated kinase signaling pathways. These findings highlight SARDH and CXCL1 as critical regulators of tumor cell behavior and offer new insights into developing targeted cancer therapies.
