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In this study, transcriptomic data from a large cohort of CC samples and a limited number of normal controls from the TCGA database were used to construct a multigene prognostic risk model using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses. The expression of key prognostic genes, including immunoglobulin superfamily member 9 (IGSF9), was further validated in CC tissues by PCR and Western blotting. Functional assays were performed in HCT116 cells to investigate the biological effects of IGSF9 overexpression and its regulatory relationship with p53. The prognostic model identified IGSF9 as a gene significantly associated with patient survival. Although IGSF9 expression was reduced at both the mRNA and protein levels in CC tissues, its overexpression in vitro markedly promoted apoptosis, alleviated DNA damage, and suppressed cell migration and invasion. Notably, silencing of p53 partially reversed the tumor\u2010suppressive effects induced by IGSF9 overexpression, indicating that IGSF9 exerts its biological functions in a p53\u2010dependent manner. Collectively, these findings demonstrate that IGSF9 acts as a tumor suppressor in colorectal cancer and regulates DNA damage responses and apoptosis through a mechanism partially dependent on p53, highlighting its potential value as a prognostic biomarker and therapeutic target in CC.<\/jats:p>","DOI":"10.1002\/jbt.70678","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T08:36:45Z","timestamp":1768293405000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["P53 Inhibition Diminishes IGSF9 Gene Activity to Promote DNA Repair and Exacerbate the Progression of Colon Cancer"],"prefix":"10.1002","volume":"40","author":[{"given":"Huan\u2010yu","family":"Zhang","sequence":"first","affiliation":[{"name":"Teaching Management Section Affiliated Hospital of Yunnan University Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Tian","sequence":"additional","affiliation":[{"name":"Oncology Affiliated Hospital of Yunnan University Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wan\u2010fu","family":"Zhang","sequence":"additional","affiliation":[{"name":"General Surgery Affiliated Hospital of Yunnan University Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying\u2010hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Gastroenterology Affiliated Hospital of Yunnan University Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia\u2010li","family":"Feng","sequence":"additional","affiliation":[{"name":"Oncology Affiliated Hospital of Yunnan University Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Sheng","sequence":"additional","affiliation":[{"name":"Gastroenterology Affiliated Hospital of Yunnan University Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8046-2245","authenticated-orcid":false,"given":"Xue\u2010qin","family":"Shang","sequence":"additional","affiliation":[{"name":"Teaching Management Section Affiliated Hospital of Yunnan University Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2017.05.006"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2020.12.003"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2016.165"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/15330338231178403"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-020-01287-2"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3233\/CBM-210222"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/jmcb\/mjy075"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202204599"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2005.04.013"},{"issue":"20","key":"e_1_2_10_11_1","first-page":"7660","article-title":"Neither p21WAF1 nor 14\u20103\u20103Sigma Prevents G2 Progression to Mitotic Catastrophe in Human Colon Carcinoma Cells After DNA Damage, but p21WAF1 Induces Stable G1 Arrest in Resulting Tetraploid Cells","volume":"61","author":"Andreassen P. 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