PRMT1 and YBX1 Cooperatively Transcriptionally Activate GPX4 to Inhibit Ferroptosis and Promote Breast Cancer Progression.

Authors

Yu Li, Baowen Yuan, Jiaxiang Liu, Xin Wang, Jingyao Zhang, Ting Hu, Tianyu Ma, Die Zhang, Yinuo Wang, Jingjing Zhang, Jiayi Gao, Tianyang Gao, Xinhui Hao, Chang Guo, Dong Yan, Wei Huang, Yan Wang

Published in

Cancer letters. Pages 218849. Sep 22, 2026. Epub Sep 22, 2026.

Abstract

Ferroptosis, a regulated form of cell death driven by lipid peroxide accumulation, is crucial in tumor development and controlled by Glutathione Peroxidase 4 (GPX4). Targeting ferroptosis offers a promising cancer therapy approach but remains challenging. Here we show that Protein Arginine Methyltransferase 1 (PRMT1) is highly expressed in breast cancer and forms a transcriptional activation complex with Y-box binding protein 1 (YBX1). This complex binds the GPX4 promoter, suppressing ferroptosis and promoting breast cancer growth and metastasis. YBX1 recruits PRMT1 independently of its enzymatic activity, while PRMT1's methyltransferase function activates transcription via H4R3me2a modification. Combined treatment with MS023 (a type I PRMT inhibitor targeting PRMT1) and SU056 (a YBX1 inhibitor) synergistically decreases GPX4 expression, enhances ferroptosis, and suppresses tumor growth. These findings establish the PRMT1-YBX1-GPX4 axis as a previously unrecognized transcriptional regulatory module and a promising therapeutic target for breast cancer.

PMID:
42772505
Bibliographic data and abstract were imported from PubMed on 23 Sep 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.