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<p>Bladder cancer (BLCA) is a urinary system malignant tumor with high morbidity and mortality worldwide. There is an urgent need for new biomarkers and therapeutic targets. By integrating single-cell RNA sequencing, MitoCarta database and the Cancer Genome Atlas data, this study found that mitochondrial ribosomal protein L37 (MRPL37) was significantly up-regulated in BLCA, and its expression level was related to disease progression and poor prognosis. Functional experiments in vitro and in vivo confirmed that knockdown of MRPL37 could inhibit the proliferation, invasion, migration, metabolism and cisplatin resistance of BLCA cells by cell experiments, mouse subcutaneous tumor model, mouse orthotopic bladder cancer model and patient-derived organoid (PDO) model. A novel MRPL37-LRPPRC-ROS-AKT signaling axis was identified: loss of MRPL37 leads to the disorder of branched-chain amino acid metabolism, down-regulates the key mitochondrial protein LRPPRC, and then causes mitochondrial membrane potential damage and reactive oxygen species accumulation, which ultimately exert anti-cancer effect by inhibiting the AKT pathway. This study not only advances the understanding of the mechanism by which mitochondrial translation defects drive tumorigenesis, but also highlights the potential of MRPL37 as a target in BLCA prognosis and targeted therapy.</p> Graphical Abstract <p></p>

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Targeting MRPL37 disrupts the pro-tumorigenic mitochondrial cascade in bladder cancer: from LRPPRC deficiency to ROS/AKT axis inhibition

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月29日

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  • Xieyuan Leng,
  • Wenhao Lu,
  • Rongbin Zhou,
  • Chengbang Wang,
  • Zuheng Wang,
  • Haodong Peng,
  • Yitong Guo,
  • Baoyu Huang,
  • Dongwei Pan,
  • Dianyu Wang,
  • Zequn Su,
  • Xuanfan Liu,
  • Xuefang Liang,
  • Tian Guo,
  • Wen Liang,
  • Wentin Chen,
  • Zihang Huang,
  • Zhe Chen,
  • Yigan Zhang,
  • Fubo Wang

摘要

Bladder cancer (BLCA) is a urinary system malignant tumor with high morbidity and mortality worldwide. There is an urgent need for new biomarkers and therapeutic targets. By integrating single-cell RNA sequencing, MitoCarta database and the Cancer Genome Atlas data, this study found that mitochondrial ribosomal protein L37 (MRPL37) was significantly up-regulated in BLCA, and its expression level was related to disease progression and poor prognosis. Functional experiments in vitro and in vivo confirmed that knockdown of MRPL37 could inhibit the proliferation, invasion, migration, metabolism and cisplatin resistance of BLCA cells by cell experiments, mouse subcutaneous tumor model, mouse orthotopic bladder cancer model and patient-derived organoid (PDO) model. A novel MRPL37-LRPPRC-ROS-AKT signaling axis was identified: loss of MRPL37 leads to the disorder of branched-chain amino acid metabolism, down-regulates the key mitochondrial protein LRPPRC, and then causes mitochondrial membrane potential damage and reactive oxygen species accumulation, which ultimately exert anti-cancer effect by inhibiting the AKT pathway. This study not only advances the understanding of the mechanism by which mitochondrial translation defects drive tumorigenesis, but also highlights the potential of MRPL37 as a target in BLCA prognosis and targeted therapy.

Graphical Abstract