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<p>RNA 5-methylcytosine (m<sup>5</sup>C) 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 m<sup>5</sup>C transcriptome maps in cervical cancer, revealing globally elevated m<sup>5</sup>C levels in tumors. By integrating spatial transcriptomics and single-cell RNA-seq, we identify SERPINB5 as a novel m<sup>5</sup>C-regulated oncogenic effector. m<sup>5</sup>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<sup>5</sup>C-deficient cells. Our study uncovers a previously unrecognized m<sup>5</sup>C–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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月11日

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  • Jiejie Liu,
  • Limin Zhou,
  • Peipei Yao,
  • Nan Zhang,
  • Xiao Guo,
  • Fei Chen,
  • Shimin Yang,
  • Xin Du,
  • Hongyun Wang,
  • You Zhou,
  • Yu Chen,
  • Li Zhou

摘要

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.