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

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.