Background:Prostate cancer (PCa) is a prevalent malignancy with a rising incidence. Advanced PCa, often resistant to therapy, remains a major clinical challenge, underscoring the need to identify novel molecular drivers.Methods:Utilizing transcriptomic data from the TCGA and GEO databases, we identifiedAPOBEC3C (A3C)as a key candidate through WGCNA, differential expression analysis, and LASSO regression. Its clinical relevance was assessed via Kaplan–Meier survival analysis. Then, we validatedA3Cexpression patterns using immunohistochemistry and Western blot in normal and malignant prostate cell lines. The functional effects ofA3Con proliferation, migration, and invasion and mechanisms of such were evaluated through in vitro gain- and loss-of-function assays (CCK-8, Ki67 staining, wound healing, Transwell, Western blot, etc.).Results:A3Cwas significantly downregulated in PCa, and this low expression strongly correlated with adverse clinicopathological features, including advanced T stage, higher Gleason scores, and worse survival. Bioinformatically, highA3Cexpression was associated with an activated anti-tumor immune microenvironment, characterized by enhanced CD8+ T cell infiltration, reduced M2 macrophage abundance, and upregulation of the immune checkpointCD40. In vitro,A3Coverexpression effectively suppressed PCa cell proliferation, migration, and invasion, while its knockdown promoted these malignant phenotypes. Mechanistically,A3Cenhances the expression of theSTING1and its downstream related moleculesCaspase-1,IL-18, andIL-1β; upregulates DNA damage-protective genes (GSTP1andGPX3); and enhances the expression of cell cycle regulatorGAS1.Conclusions:This study establishesA3Cas a suppressor in PCa, which impedes tumor progression by regulating key molecules involved in cellular inflammation, cell cycle arrest, and DNA damage response.
**背景：** 前列腺癌是一种发病率不断上升的常见恶性肿瘤。晚期前列腺癌通常对治疗产生抵抗，仍是主要的临床挑战，这凸显了识别新型分子驱动因子的必要性。 **方法：** 利用来自TCGA和GEO数据库的转录组数据，我们通过加权基因共表达网络分析、差异表达分析和LASSO回归，鉴定出**APOBEC3C** 作为一个关键候选基因。通过Kaplan-Meier生存分析评估其临床相关性。随后，我们使用免疫组织化学和蛋白质印迹法在正常和恶性前列腺细胞系中验证了**A3C** 的表达模式。通过体外功能获得和功能缺失实验，评估了**A3C** 对细胞增殖、迁移和侵袭的功能影响及其机制。 **结果：** **A3C** 在前列腺癌中显著下调，这种低表达与不良的临床病理特征密切相关，包括更高的T分期、更高的格里森评分以及更差的生存期。生物信息学分析显示，高**A3C** 表达与活化的抗肿瘤免疫微环境相关，其特征是CD8+ T细胞浸润增强、M2巨噬细胞丰度降低以及免疫检查点**CD40** 上调。在体外，**A3C** 过表达有效抑制了前列腺癌细胞的增殖、迁移和侵袭，而其敲低则促进了这些恶性表型。机制上，**A3C** 增强了**STING1** 及其下游相关分子**Caspase-1**、**IL-18** 和**IL-1β** 的表达；上调了DNA损伤保护基因；并增强了细胞周期调节因子**GAS1** 的表达。 **结论：** 本研究确立了**A3C** 在前列腺癌中的抑癌作用，它通过调控参与细胞炎症、细胞周期阻滞和DNA损伤反应的关键分子来阻碍肿瘤进展。
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