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<p>Hypoxia is a hallmark of tumor microenvironments that promotes bladder cancer (BCa). We aimed to study the upstream transfector of ROC1 on malignant oncological characteristics of BCa cells under hypoxic conditions, and clarified the regulating mechanisms involved.&#xa0;The expressions of ROC1 and HIF1A were mediated by RT-qPCR and western blot. The upstream transcription factor of ROC1 was analyzed by bioinformatic analysis and examined by clinical data. The BCa cell lines (T24 and 5637) were treated CREB1 overexpression or knockdown. The hypoxia induction was conducted, and cell proliferation, apoptosis, migration and invasion were subsequently studied. The rescue experiments in vitro and in vivo were performed to explore the underlying regulating mechanism of CREB1.&#xa0;ROC1 was down-regulated in bladder cancer tissues and hypoxia condition. CREB1 was an upstream transcription factor of ROC1. CREB1 expression was correlated with T Stage in BCa, while ROC1expression was associated with N Stage in BCa patients. CREB1 promoted the proliferation and inhibited the apoptosis of BCa cells under hypoxia. CREB1 regulated the invasion, migration, and expressions of Bcl−2, Bax, cleaved caspased−3, MMP2, and MMP9 in BCa cells under hypoxia. Down-regulation of ROC1 reversed CREB1’s effect on BCa cells. Similarly, HIF1A knockdown also reversed CREB1’s impact on BCa cells. CREB1 promoted tumor growth in vivo and shROC1 reversed its effect.&#xa0;Our study indicated that CREB1-ROC1 axis is a hypoxia-responsive therapeutic target in BCa, which can provide new insights for BCa early screening, prevention and treatment.</p> Graphical abstract <p></p>

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CREB1-ROC1 axis drives bladder cancer progression under hypoxic conditions

  • 期刊论文

  • 发表日期：

    2026年4月4日

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  • Zhenchao Sun,
  • Yingyu Wang,
  • Shengjie You,
  • Qingfen Ji,
  • Xiang Liu,
  • Pengfei Bao,
  • Huijiang Zhang,
  • Xiaoqing Zhou,
  • Junjie Ye,
  • Peng Li,
  • Qi Wu

摘要

Hypoxia is a hallmark of tumor microenvironments that promotes bladder cancer (BCa). We aimed to study the upstream transfector of ROC1 on malignant oncological characteristics of BCa cells under hypoxic conditions, and clarified the regulating mechanisms involved. The expressions of ROC1 and HIF1A were mediated by RT-qPCR and western blot. The upstream transcription factor of ROC1 was analyzed by bioinformatic analysis and examined by clinical data. The BCa cell lines (T24 and 5637) were treated CREB1 overexpression or knockdown. The hypoxia induction was conducted, and cell proliferation, apoptosis, migration and invasion were subsequently studied. The rescue experiments in vitro and in vivo were performed to explore the underlying regulating mechanism of CREB1. ROC1 was down-regulated in bladder cancer tissues and hypoxia condition. CREB1 was an upstream transcription factor of ROC1. CREB1 expression was correlated with T Stage in BCa, while ROC1expression was associated with N Stage in BCa patients. CREB1 promoted the proliferation and inhibited the apoptosis of BCa cells under hypoxia. CREB1 regulated the invasion, migration, and expressions of Bcl−2, Bax, cleaved caspased−3, MMP2, and MMP9 in BCa cells under hypoxia. Down-regulation of ROC1 reversed CREB1’s effect on BCa cells. Similarly, HIF1A knockdown also reversed CREB1’s impact on BCa cells. CREB1 promoted tumor growth in vivo and shROC1 reversed its effect. Our study indicated that CREB1-ROC1 axis is a hypoxia-responsive therapeutic target in BCa, which can provide new insights for BCa early screening, prevention and treatment.

Graphical abstract