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<p>Bladder cancer (BCa) remains a challenging malignancy due to its capacity for immune evasion and therapy resistance. This study comprehensively investigates the tumor-suppressive microRNA hsa-miR-145-3p using multi-omics data from the TCGA-BLCA cohort. We found that hsa-miR-145-3p is significantly downregulated in BCa tissues, and its low expression independently predicts advanced tumor stage, lymph node metastasis, and poor overall survival. Functional analyses revealed that hsa-miR-145-3p loss reshapes the tumor immune microenvironment by reducing CD8⁺ T cells and dendritic cells while increasing immunosuppressive M2 macrophages, Tregs, and neutrophils, leading to elevated stromal scores and TIDE-based immunotherapy resistance. Mechanistically, it targets key genes (e.g., ANO9, RAD54B, SRSF6) and modulates pathways including spliceosome, cell cycle, and PD-1/PD-L1 signaling. Low expression also confers resistance to gemcitabine/cisplatin but enhances susceptibility to Dasatinib. We conclude that hsa-miR-145-3p is a central immunoregulator and a promising biomarker for prognosis and therapy selection in BCa.</p>

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hsa-miR-145-3p defines a fibro-inflammatory bladder cancer subtype with distinct therapeutic vulnerabilities

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月28日

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  • Muyang Xu,
  • Shaoyu Yue,
  • Ziqi Chen,
  • Rongrong Li,
  • Jing Chen,
  • Chaozhao Liang

摘要

Bladder cancer (BCa) remains a challenging malignancy due to its capacity for immune evasion and therapy resistance. This study comprehensively investigates the tumor-suppressive microRNA hsa-miR-145-3p using multi-omics data from the TCGA-BLCA cohort. We found that hsa-miR-145-3p is significantly downregulated in BCa tissues, and its low expression independently predicts advanced tumor stage, lymph node metastasis, and poor overall survival. Functional analyses revealed that hsa-miR-145-3p loss reshapes the tumor immune microenvironment by reducing CD8⁺ T cells and dendritic cells while increasing immunosuppressive M2 macrophages, Tregs, and neutrophils, leading to elevated stromal scores and TIDE-based immunotherapy resistance. Mechanistically, it targets key genes (e.g., ANO9, RAD54B, SRSF6) and modulates pathways including spliceosome, cell cycle, and PD-1/PD-L1 signaling. Low expression also confers resistance to gemcitabine/cisplatin but enhances susceptibility to Dasatinib. We conclude that hsa-miR-145-3p is a central immunoregulator and a promising biomarker for prognosis and therapy selection in BCa.