{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T15:51:02Z","timestamp":1789487462119,"version":"build-2803163510"},"reference-count":20,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T00:00:00Z","timestamp":1784419200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T00:00:00Z","timestamp":1784419200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2025J01791"],"award-info":[{"award-number":["2025J01791"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>In this investigation, we examined the functional mechanism of the transcription factor zinc finger protein 695 (ZNF695) and its target gene chromobox protein homolog 8 (CBX8) in colorectal cancer (CRC) migration and invasion. HCT\u2010116 and LOVO cell lines were used to establish cell models with knocked\u2010down ZNF695 and knocked\u2010down or over\u2010expressed CBX8. To comprehensively evaluate the functional contributions of ZNF695 and CBX8 to cellular phenotypes, we employed CCK\u20108, wound\u2010healing, and Transwell assays to evaluate cell proliferation, migration, and invasion, respectively. To assess the impact of ZNF695 on tumor progression, we generated a xenograft model utilizing nude mice. A FLAG\u2010ZNF695 expression plasmid was constructed, and ChIP\u2010seq experiments were performed. By integrating mRNA sequencing data following ZNF695 knockdown with highly expressed genes in CRC from the TCGA database, CBX8 was identified as a putative downstream target of ZNF695. We employed a dual\u2010luciferase reporter assay to validate the specific binding affinity of ZNF695 toward the CBX8 promoter region. To elucidate the specific biological cascades modulated by ZNF695 and CBX8, we conducted a comprehensive pathway enrichment analysis. Rescue experiments were conducted to determine whether the ZNF695\/CBX8 regulatory axis upregulates the expression of the Wnt signaling pathway downstream targets, AXIN2 and CCND1. Both in vitro assays and in vivo models confirmed that silencing ZNF695 dramatically suppresses CRC cell proliferation, migration, and invasion, while concurrently impeding tumor progression. ChIP\u2010seq coupled with dual\u2010luciferase reporter assays substantiated the direct binding of ZNF695 to the CBX8 promoter. Furthermore, CBX8 depletion significantly attenuated the migratory and invasive phenotypes of CRC cells. Restoring CBX8 expression effectively rescued the migratory and invasive deficits in CRC cells induced by ZNF695 silencing. Re\u2010expression of CBX8 in ZNF695\u2010silenced cells restored Wnt\/\u03b2\u2010catenin signaling activity, accompanied by increased expression of AXIN2 and CCND1. ZNF695 promotes CRC progression by transcriptionally activating CBX8 and subsequently enhancing Wnt\/\u03b2\u2010catenin signaling, thereby promoting tumor cell proliferation, migration, and invasion.<\/jats:p>","DOI":"10.1002\/mc.70154","type":"journal-article","created":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T14:45:48Z","timestamp":1784472348000},"page":"1183-1193","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ZNF695 Promotes Colorectal Cancer Progression Through Transcriptional Activation of CBX8 and Subsequent Wnt\/\u03b2\u2010Catenin Signaling Activation"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6491-8190","authenticated-orcid":false,"given":"Xiaozhun","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Colorectal Surgery Fujian Medical University Union Hospital Fuzhou China"},{"name":"Department of Otolaryngology Head and Neck Surgery The Affiliated Cancer Hospital of Guangxi Medical University Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailin","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery Fujian Medical University Union Hospital Fuzhou China"},{"name":"Department of Gastrointestinal Surgery The Second Affiliated Hospital of Xiamen Medical College Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3117-145X","authenticated-orcid":false,"given":"Ying","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery Fujian Medical University Union Hospital Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.70067"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2025.06.089"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32319-0"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0043-1761447"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21155255"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.100"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12082296"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14215242"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-025-07585-1"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2025.8949"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.881262"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.2174\/0113892037273375231204080906"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.2174\/0115665232285216240228071244"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-014-1841-x"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1016683"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes10090716"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.115.180125"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/1757-2215-6-61"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2023.5484"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omto.2020.09.012"}],"container-title":["Molecular 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