M5C-driven stabilization of SERPINB5 promotes cervical cancer progression and chemotherapy resistance

Liu, Jiejie, Zhou, Limin, Yao, Peipei, Zhang, Nan, Guo, Xiao, Chen, Fei, Yang, Shimin, Du, Xin, Wang, Hongyun, Zhou, You ORCID: https://orcid.org/0000-0002-1743-1291, Chen, Yu and Zhou, Li 2026. M5C-driven stabilization of SERPINB5 promotes cervical cancer progression and chemotherapy resistance. Cell Death & Disease 17 , 215. 10.1038/s41419-026-08453-2

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Abstract

RNA 5-methylcytosine (m5C) plays a critical role in cancer, yet its functional mechanisms and therapeutic relevance in cervical cancer remain unclear. Here, we generate the first base-resolution m5C transcriptome maps in cervical cancer, revealing globally elevated m5C levels in tumors. By integrating spatial transcriptomics and single-cell RNA-seq, we identify SERPINB5 as a novel m5C-regulated oncogenic effector. m5C modification enhances SERPINB5 mRNA stability and protein expression, promoting tumor growth, metastasis, and resistance to microtubule-targeting chemotherapeutics. Mechanistically, SERPINB5 upregulates mitotic regulators and microtubule motor proteins, including CENPE, enhancing mitotic progression and counteracting drug-induced mitotic arrest. Loss-of-function experiments demonstrate that SERPINB5 depletion sensitizes cervical cancer cells to paclitaxel and vincristine, while its reintroduction restores chemoresistance even in m5C-deficient cells. Our study uncovers a previously unrecognized m5C–SERPINB5 axis as a central driver of cervical cancer malignancy and chemoresistance, highlighting SERPINB5 as a clinically actionable target to improve outcomes for patients receiving microtubule-targeting chemotherapy.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Publisher:	Springer Nature [academic journals on nature.com]
Date of First Compliant Deposit:	23 February 2026
Date of Acceptance:	28 January 2026
Last Modified:	23 Feb 2026 11:45
URI:	https://orca.cardiff.ac.uk/id/eprint/185104

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