{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T03:25:22Z","timestamp":1778642722087,"version":"3.51.4"},"reference-count":44,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T00:00:00Z","timestamp":1767398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"publisher","award":["YQ2024H012"],"award-info":[{"award-number":["YQ2024H012"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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 identified APOBEC3C (A3C) as a key candidate through WGCNA, differential expression analysis, and LASSO regression. Its clinical relevance was assessed via Kaplan\u2013Meier survival analysis. Then, we validated A3C expression patterns using immunohistochemistry and Western blot in normal and malignant prostate cell lines. The functional effects of A3C on 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:A3C was 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, high A3C expression 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 checkpoint CD40. In vitro, A3C overexpression effectively suppressed PCa cell proliferation, migration, and invasion, while its knockdown promoted these malignant phenotypes. Mechanistically, A3C enhances the expression of the STING1 and its downstream related molecules Caspase-1, IL-18, and IL-1\u03b2; upregulates DNA damage-protective genes (GSTP1 and GPX3); and enhances the expression of cell cycle regulator GAS1. Conclusions: This study establishes A3C as a suppressor in PCa, which impedes tumor progression by regulating key molecules involved in cellular inflammation, cell cycle arrest, and DNA damage response.<\/jats:p>","DOI":"10.3390\/cancers18010170","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T10:03:48Z","timestamp":1767607428000},"page":"170","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["APOBEC3C Suppresses Prostate Cancer by Regulating Key Molecules Involved in Cellular Inflammation, Cell Cycle Arrest, and DNA Damage Response"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5730-4967","authenticated-orcid":false,"given":"Zhongqi","family":"Pang","sequence":"first","affiliation":[{"name":"Department of Urology, First Affiliated Hospital of Harbin Medical University, Harbin 150001, China"},{"name":"Department of Pancreatic and Biliary Surgery, First Affiliated Hospital of Harbin Medical University, Harbin 150001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3032-9379","authenticated-orcid":false,"given":"Jianshe","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology, First Affiliated Hospital of Harbin Medical University, Harbin 150001, China"},{"name":"Department of Urology, Yinfeng (Jinan) Hospital, Jinan 250014, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5550-9811","authenticated-orcid":false,"given":"Yidan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin 150001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6771-2817","authenticated-orcid":false,"given":"Bo","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Urology, First Affiliated Hospital of Harbin Medical University, Harbin 150001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8736-1180","authenticated-orcid":false,"given":"Minghua","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Urology, First Affiliated Hospital of Harbin Medical University, Harbin 150001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beichen","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Urology, First Affiliated Hospital of Harbin Medical University, Harbin 150001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,3]]},"reference":[{"key":"ref_1","first-page":"7","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J. 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