Yin Yang 1 activates JAK-STAT3-mediated epithelial-mesenchymal transition in Helicobacter pylori-induced gastric cancer progression

doi:10.5306/wjco.v16.i12.112626

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World Journal of Clinical Oncology

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World J Clin Oncol. Dec 24, 2025; 16(12): 112626
Published online Dec 24, 2025. doi: 10.5306/wjco.v16.i12.112626

Yin Yang 1 activates JAK-STAT3-mediated epithelial-mesenchymal transition in Helicobacter pylori-induced gastric cancer progression

Jing-Wan Chen, Jie-Ji Ouyang, Zhen-Hui Wang, Di-Meng Ma, Zhi Zhang, Qiong Teng, Gang Yu, Xiang-Yong Li

Jing-Wan Chen, Zhen-Hui Wang, Di-Meng Ma, Zhi Zhang, Qiong Teng, Xiang-Yong Li, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China

Jing-Wan Chen, Jie-Ji Ouyang, Gang Yu, Department of General Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China

Co-first authors: Jing-Wan Chen and Jie-Ji Ouyang.

Co-corresponding authors: Gang Yu and Xiang-Yong Li.

Author contributions: Chen WJ, Ouyang JJ, and Yu G were responsible for manuscript writing; Chen JW and Ouyang JJ contributed equally to this article as the co-first authors; Wang ZH and Ma MD were responsible for assistance in cell function experiments and clinical data compilation; Zhang Z and Teng Q were responsible for clinical data collection and analysis; Yu G and Li XY were responsible for concept and design and supervision, and they contributed equally to this article as the co-corresponding authors; and all authors have read and approved the manuscript.

Supported by the National Natural Science Foundation of China, No. 82372646; and Research Fund of Anhui Institute of Translational Medicine, No. 2023zhyx-C70 and No. 2023zhyx-C80.

Institutional review board statement: This study was approved by the Medical Ethics Committee of The Anhui Medical University (approval No. 20180323).

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 Anhui Medical University (approval No. LLSC20180345).

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.

Data sharing statement: No additional data are available.

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: Xiang-Yong Li, PhD, Chief Physician, Professor, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Shushan District, Hefei 230022, Anhui Province, China. liyongxiang@ahmu.edu.cn

Received: August 4, 2025
Revised: September 9, 2025
Accepted: November 13, 2025
Published online: December 24, 2025
Processing time: 143 Days and 23.7 Hours

Abstract

BACKGROUND

Helicobacter pylori (H. pylori) infection is widely considered to be a major risk factor for gastric cancer, contributing to its development through the Correa cascade. Yin Yang 1 (YY1) is a transcription factor that acts as a promoter or suppressor of cancer progression. However, the role of YY1 in the inflammatory transformation associated with H. pylori-induced gastric cancer remains unclear.

AIM

To explore the expression of YY1 in gastric cancer and its impact on cancer progression with H. pylori infection.

METHODS

H. pylori bacteria were cocultured with GSE1 cells, AGS cells, and SGC7901 cells, as well as in infected and xenograft mouse models. Expression of YY1, members of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway, and epithelial-mesenchymal transition (EMT)-related proteins in gastric cancer was examined using Western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry. Survival analysis was performed using the Kaplan-Meier method with the log-rank test. The role of YY1 in gastric cancer cell proliferation was further evaluated through in vitro and in vivo assays.

RESULTS

YY1 was highly expressed in gastric cancer tissues and cells. Kaplan-Meier survival curves indicated that high YY1 expression correlated with a poor prognosis. YY1 expression showed a gradually increasing trend in H. pylori-induced gastritis and gastric tumors. In vivo and in vitro experiments demonstrated that H. pylori infection promoted phosphorylation of JAK2 and STAT3, thereby activating the EMT pathway, in which YY1 played a key role. YY1 and JAK2 interaction was validated by chromatin immunoprecipitation. YY1 knockdown or pharmacological inhibition reversed EMT and suppressed gastric cancer cell proliferation and metastasis.

CONCLUSION

These results suggest that YY1 plays an important role in progression of H. pylori-induced gastric cancer by activating EMT.

Keywords: Helicobacter pylori; Gastric cancer; Yin Yang 1; Janus kinase 2/signal transducer and activator of transcription 3; Epithelial-mesenchymal transition

Core Tip: This study revealed that Yin Yang 1 (YY1) was upregulated in Helicobacter pylori-induced gastritis and gastric cancer, where it promoted tumor proliferation, invasion, epithelial-mesenchymal transition, and growth by directly activating Janus kinase 2 transcription and enhancing Janus kinase 2/signal transducer and activator of transcription 3 phosphorylation. YY1 knockdown or pharmacological inhibition reversed these malignant phenotypes. These findings elucidate a key mechanistic pathway in gastric carcinogenesis and identify YY1 as a potential therapeutic target for Helicobacter pylori-associated malignancy.