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

## TL;DR

This study finds that RNA m5C modification stabilizes SERPINB5, promoting cervical cancer growth and resistance to chemotherapy.

## Contribution

The first base-resolution m5C transcriptome maps in cervical cancer and identification of SERPINB5 as an m5C-regulated oncogenic effector.

## Key findings

- SERPINB5 mRNA stability and protein expression are enhanced by m5C modification, promoting tumor growth and metastasis.
- SERPINB5 upregulates mitotic regulators like CENPE, counteracting drug-induced mitotic arrest.
- SERPINB5 depletion sensitizes cervical cancer cells to chemotherapeutics like paclitaxel and vincristine.

## 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.