Scholarlink

<p>Bladder cancer remains a clinically challenging malignancy, with increasing evidence suggesting that chronic bladder inflammation, such as interstitial cystitis (IC), may contribute to its development. However, the molecular mechanisms linking inflammation to tumorigenesis are poorly understood. Here, we identify coiled-coil domain-containing 8 (CCDC8) as a potential oncogenic factor in bladder cancer. Transcriptomic analysis revealed that CCDC8 is dysregulated in both IC and bladder cancer, with overexpression confirmed in tumor tissues and cell lines. Elevated CCDC8 expression was significantly associated with advanced tumor stage, lymph node metastasis, and poor prognosis, particularly in patients harboring wild-type TP53. Functional studies demonstrated that CCDC8 promotes tumor cell proliferation, migration, and survival in vitro, and enhances tumor growth in vivo. Mechanistically, CCDC8 interacts with the E3 ubiquitin ligase scaffold protein CUL7, facilitating proteasome-dependent degradation of P53, thereby suppressing its downstream effectors such as P21 and BAX. Pharmacological inhibition of neddylation with MLN4924 restored P53 levels and reversed the oncogenic effects of CCDC8 both in vitro and in vivo. Together, these findings highlight a novel mechanism of P53 regulation in bladder cancer, position CCDC8 as a potential biomarker and therapeutic target, and suggest a molecular link between chronic bladder inflammation and malignant transformation.</p><p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Interstitial cystitis-related gene CCDC8 accelerates tumorigenesis by participating in CUL7-mediated degradation of P53 in bladder cancer

  • 期刊论文

  • 发表日期：

    2026年2月5日

查看全文
  • Jiawen Wang,
  • Jinfu Wang,
  • Lingfeng Meng,
  • Xinhao Wang,
  • Zehao Yan,
  • Honghong Pan,
  • Jiayue Wu,
  • Qidong Zhou,
  • Liefu Ye,
  • Jinfeng Wu,
  • Yaoguang Zhang,
  • Jianye Wang

摘要

Bladder cancer remains a clinically challenging malignancy, with increasing evidence suggesting that chronic bladder inflammation, such as interstitial cystitis (IC), may contribute to its development. However, the molecular mechanisms linking inflammation to tumorigenesis are poorly understood. Here, we identify coiled-coil domain-containing 8 (CCDC8) as a potential oncogenic factor in bladder cancer. Transcriptomic analysis revealed that CCDC8 is dysregulated in both IC and bladder cancer, with overexpression confirmed in tumor tissues and cell lines. Elevated CCDC8 expression was significantly associated with advanced tumor stage, lymph node metastasis, and poor prognosis, particularly in patients harboring wild-type TP53. Functional studies demonstrated that CCDC8 promotes tumor cell proliferation, migration, and survival in vitro, and enhances tumor growth in vivo. Mechanistically, CCDC8 interacts with the E3 ubiquitin ligase scaffold protein CUL7, facilitating proteasome-dependent degradation of P53, thereby suppressing its downstream effectors such as P21 and BAX. Pharmacological inhibition of neddylation with MLN4924 restored P53 levels and reversed the oncogenic effects of CCDC8 both in vitro and in vivo. Together, these findings highlight a novel mechanism of P53 regulation in bladder cancer, position CCDC8 as a potential biomarker and therapeutic target, and suggest a molecular link between chronic bladder inflammation and malignant transformation.