ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1585236
This article is part of the Research TopicRenewed Insight into Cancer Mechanism and TherapyView all 29 articles
Targeting GJB4 to Inhibit Tumor Growth and Induce Ferroptosis in Pancreatic Cancer
Provisionally accepted
- 1Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
- 2Chongqing Medical University, Chongqing, China
- 3Department of Medicine, Huddinge, Karolinska Institutet (KI), Huddinge, Stockholm, Sweden
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Pancreatic cancer (PC) is a highly malignant type of cancer characterized by poor prognosis and high mortality rate. The role of gap junction protein beta 4 (GJB4) in PC has been scarcely reported. Therefore, the aim of this study was to investigate the function of GJB4 in PC cells and its potential as a therapeutic target.The expression of GJB4 in patients with PC was examined using data from The Cancer Genome Atlas (TCGA), The Human Protein Atlas, Gene Expression Omnibus (GEO), Tumor Immune Estimation Resource (TIMER), microRNA Target Prediction Database (miRDB), and Encyclopedia of RNA Interactomes (ENCORI). A short hairpin-RNA lentiviral vector was employed to downregulate GJB4 in PC cells. The effects on tumor cell proliferation, invasion, and metastasis were assessed using cell proliferation assays, Transwell migration assays, wound healing assays, and subcutaneous xenograft models. Bioinformatics analysis was conducted to explore the function of GJB4 in PC cells. Changes in ferroptosis in PC cells following GJB4 downregulation were detected by immunofluorescence staining, transmission electron microscopy, and western blotting.GJB4 expression was found to be upregulated in PC tissues and positively correlated with patient survival. The expression of GJB4 was related to immune cell infiltration, tumor mutational burden expression and miRNAs. Downregulation of GJB4 inhibited the proliferation, metastasis, and invasion of PC cells, as well as tumor growth in nude mouse subcutaneous xenografts. Knockdown of GJB4 in PC cells disrupted oxidative and iron ion balance, and promoted ferroptosis, thereby inhibiting tumorigenic properties.The findings of this study indicate that downregulation of GJB4 may suppress tumor characteristics by promoting ferroptosis in PC cells. Therefore, GJB4 may be a promising 3 therapeutic target for the treatment of PC.
Keywords: Pancreatic Cancer, GJB4, Reactive Oxygen Species, ferroptosis, Bioinformactics
Received: 28 Feb 2025; Accepted: 27 May 2025.
Copyright: © 2025 Zheng, Li, Li, Yao, Zheng, Fan and Bie. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ping Bie, Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.