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ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Molecular Diagnostics and Therapeutics
Volume 12 - 2025 |
doi: 10.3389/fmolb.2025.1542650
An unfolded protein response (UPR)-signature regulated by NFKB-miR-29b/c axis fosters tumor aggressiveness and poor survival in bladder cancer
Provisionally accepted
Jian Zhang 1 Xiaosong Fan 1 Yu Chen 2 Yichao Han 3 Weixing Yu 1 Shaolin Zhang 4 Bicheng Yang 3 Junlong Zhang 3
Yanling Chen 5*- 1 Department of Urology, Shangyu People's Hospital of Shaoxing, Shaoxing, Zhejiang Province, China
- 2 Zhejiang Hisoar Pharmaceutical Co Ltd, Hangzhou, China
- 3 Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- 4 Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui Province, China
- 5 Digestive Endoscopy Center, The First Affiliated Hospital of Wannan Medical College, Wuhu, China
Bladder cancer continues to pose a substantial global health challenge, marked by a high mortality rate despite advances in treatment options. Therefore, in-depth understanding of molecular mechanisms related to disease onset, progression, and patient survival is of utmost importance in bladder cancer research. In this study, we employed a stringent differential expression and survival analyses-based pipeline to investigate the underlying molecular mechanisms, and identified elevated endoplasmic reticulum (ER) stress response as key culprit in bladder cancer. Pathway enrichment and network analyses led us to construct an eight-gene unfolded protein response (UPR)-related gene signature (UPR-GS) that determines aggressive disease state and poor survival in bladder cancer patients. Notably, elevated UPR-GS is attributed to downregulation of two miRNAs from the miR-29 family (miR-29b-2-5p and miR-29c-5p) that exhibit potential to limit UPR-driven tumor aggressiveness and determine good survival in bladder cancer. At further upstream, inflammation-related NFKB transcription factor inhibits miR-29b/c expression, driving UPR-related tumor progression, and determining poor survival in bladder cancer patients. Overall, these findings highlight that aberrantly activated UPR, regulated by NFKB-miR-29b/c axis plays a crucial role in tumor aggressiveness and disease progression in bladder cancer, highlighting potential targets for therapeutic interventions and prognostic markers in bladder cancer management.
Keywords: Bladder cancer, er stress, upr, Inflammation, NFkB, miR-29b/c
Received: 12 Dec 2024; Accepted: 20 Jan 2025.
Copyright: © 2025 Zhang, Fan, Chen, Han, Yu, Zhang, Yang, Zhang and Chen. 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:
Yanling Chen, Digestive Endoscopy Center, The First Affiliated Hospital of Wannan Medical College, Wuhu, China
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