Silencing HOXC13 exerts anti-prostate cancer effects by inducing DNA damage and activating cGAS/STING/IRF3 pathway

作者：Maozhang Li, Guangwei Bai, Yi Cen, Qitong Xie, Jiahong Chen, Jia Chen, Qing-Biao Chen, Weide Zhong, Xiaobo Zhou · 发表于：Journal of Translational Medicine · 年份：2023 · DOI：10.1186/s12967-023-04743-x · 被引用次数：20 · 研究领域：interferon and immune responses、Ferroptosis and cancer prognosis、Cancer-related molecular mechanisms research

BACKGROUND: Advanced prostate cancer (PCa) will develop into castration-resistant prostate cancer (CRPC) and lead to poor prognosis. As the primary subtype of CRPC, CRPC-AR accounts for the major induction of PCa heterogeneity. CRPC-AR is mainly driven by 25 transcription factors (TFs), which we speculate may be the key factors driving PCa toward CRPC. Therefore, it is necessary to clarify the key regulator and its molecular mechanism mediating PCa progression. METHODS: Firstly, we downloaded transcriptomic data and clinical information from TCGA-PRAD. The characteristic gene cluster was identified by PPI clustering, GO enrichment, co-expression correlation and clinical feature analyses for 25 TFs. Then, the effects of 25 TFs expression on prognosis of PCa patients was analyzed using univariate Cox regression, and the target gene was identified. The expression properties of the target gene in PCa tissues were verified using tissue microarray. Meanwhile, the related mechanistic pathway of the target gene was mined based on its function. Next, the target gene was silenced by small interfering RNAs (siRNAs) for cellular function and mechanistic pathway validation. Finally, CIBERSORT algorithm was used to analyze the infiltration levels of 22 immune cells in PCa patients with low and high expression of target gene, and validated by assaying the expression of related immunomodulatory factor. RESULTS: We found that HOX family existed independently in 25 TFs, among which HOXC10, HOX...