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Here, we generate the first base-resolution m\n                    <jats:sup>5<\/jats:sup>\n                    C transcriptome maps in cervical cancer, revealing globally elevated m\n                    <jats:sup>5<\/jats:sup>\n                    C levels in tumors. By integrating spatial transcriptomics and single-cell RNA-seq, we identify SERPINB5 as a novel m\n                    <jats:sup>5<\/jats:sup>\n                    C-regulated oncogenic effector. m\n                    <jats:sup>5<\/jats:sup>\n                    C 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 m\n                    <jats:sup>5<\/jats:sup>\n                    C-deficient cells. Our study uncovers a previously unrecognized m\n                    <jats:sup>5<\/jats:sup>\n                    C\u2013SERPINB5 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.\n                  <\/jats:p>","DOI":"10.1038\/s41419-026-08453-2","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T08:17:48Z","timestamp":1770797868000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["M5C-driven stabilization of SERPINB5 promotes cervical cancer progression and chemotherapy resistance"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5442-6471","authenticated-orcid":false,"given":"Jiejie","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peipei","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6237-5595","authenticated-orcid":false,"given":"Hongyun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1743-1291","authenticated-orcid":false,"given":"You","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1300-4652","authenticated-orcid":false,"given":"Yu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6736-0057","authenticated-orcid":false,"given":"Li","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"8453_CR1","first-page":"229","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. 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All human specimens, including those used for sequencing and immunohistochemical (IHC) staining, were obtained from archived samples collected during routine diagnostic procedures, imposing no additional burden on the patients. Among these, a subset of patients underwent neoadjuvant or adjuvant chemotherapy regimens based on paclitaxel. For this subset, clinical follow-up was performed for at least 6 months. Paclitaxel-resistant tumors were defined as those from patients who failed to achieve a complete clinical response (CR) following initial treatment or experienced tumor recurrence or progression within 6 months after CR. Paclitaxel-sensitive tumors were defined as those from patients with a recurrence-free interval exceeding 6 months. This classification was retrospectively determined based on clinical records, treatment responses, and follow-up data. Informed consent was obtained from all participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"215"}}