<p>Prostate cancer is one of the most prevalent malignancies in men, with increasing incidence and mortality largely attributed to treatment resistance and metastasis. The effectiveness of current therapies for advanced cases is hindered by intricate genetic and microenvironmental factors, emphasizing the urgent need for novel therapeutic targets. Chimeric RNAs have emerged as promising biomarkers in cancer research, among which CCDC7<sub>19-13</sub>, a circular chimeric RNA, is frequently identified in prostate cancer. Our study reveals that CCDC7<sub>19-13</sub> expression is markedly reduced in advanced and recurrent prostate cancer, where its low levels serve as an independent predictor of poor prognosis. Functional experiments demonstrate that CCDC7<sub>19-13</sub> overexpression inhibits cell proliferation, induces apoptosis, and suppresses tumor growth in vivo, whereas its knockdown reverses these effects. Mechanistically, CCDC7<sub>19-13</sub> encodes a novel protein, CCDC7<sub>241aa</sub>, which triggers ferroptosis by interacting with SLC7A11 and facilitating its TRIM21-mediated ubiquitination and degradation. Notably, treatment with recombinant CCDC7<sub>241aa</sub> effectively suppresses tumor growth in patient-derived xenograft models without toxicity and enhances the efficacy of docetaxel and enzalutamide in vitro. These findings establish CCDC7<sub>19-13</sub> as a significant prognostic marker and potential therapeutic target in prostate cancer, with the recombinant CCDC7<sub>241aa</sub> protein offering promise for combination therapies in advanced cases.</p><p></p>

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Induction of ferroptosis in prostate cancer by CCDC719-13 via TRIM21-mediated ubiquitination of SLC7A11

  • Bisheng Cheng,
  • Qiong Wang,
  • Zean Li,
  • Tianlong Luo,
  • JunJia Xie,
  • Sandeep Singh,
  • Yong Luo,
  • Xu Gao,
  • Hui Li,
  • Zongwei Wang,
  • Peng Wu,
  • Hai Huang

摘要

Prostate cancer is one of the most prevalent malignancies in men, with increasing incidence and mortality largely attributed to treatment resistance and metastasis. The effectiveness of current therapies for advanced cases is hindered by intricate genetic and microenvironmental factors, emphasizing the urgent need for novel therapeutic targets. Chimeric RNAs have emerged as promising biomarkers in cancer research, among which CCDC719-13, a circular chimeric RNA, is frequently identified in prostate cancer. Our study reveals that CCDC719-13 expression is markedly reduced in advanced and recurrent prostate cancer, where its low levels serve as an independent predictor of poor prognosis. Functional experiments demonstrate that CCDC719-13 overexpression inhibits cell proliferation, induces apoptosis, and suppresses tumor growth in vivo, whereas its knockdown reverses these effects. Mechanistically, CCDC719-13 encodes a novel protein, CCDC7241aa, which triggers ferroptosis by interacting with SLC7A11 and facilitating its TRIM21-mediated ubiquitination and degradation. Notably, treatment with recombinant CCDC7241aa effectively suppresses tumor growth in patient-derived xenograft models without toxicity and enhances the efficacy of docetaxel and enzalutamide in vitro. These findings establish CCDC719-13 as a significant prognostic marker and potential therapeutic target in prostate cancer, with the recombinant CCDC7241aa protein offering promise for combination therapies in advanced cases.