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As core components of the polycomb repressive complex 1 (PRC1), chromobox (CBX) proteins recognize H3K27me3 to recruit PRC1 to maintain a repressive transcriptional state. However, the individual biological functions of these CBX proteins in tumorigenesis warrant in\u2010depth investigation. In this study, we analyzed the mRNA expression of CBX family genes across multiple cancers using The Cancer Genome Atlas data and found different expression patterns of the five CBX genes in different types of cancer. This analyses together with the result of immunohistochemistry indicated that CBX8 expression was significantly higher in lung adenocarcinoma (LUAD) tissues compared to adjacent nontumor tissues. Overexpression approaches demonstrated that CBX8 facilitated LUAD cell proliferation and migration in vitro. Consistently, CBX8 knockdown reduced LUAD cell proliferation and migration in both cell culture and mouse models. RNA sequencing combined with real\u2010time RT\u2010PCR assays revealed <jats:italic>CDKN2C<\/jats:italic> and <jats:italic>SCEL<\/jats:italic> as target genes of CBX8. Furthermore, chromatin immunoprecipitation assays indicated that CBX8 directly bound to the promoters of <jats:italic>CDKN2C<\/jats:italic> and <jats:italic>SCEL<\/jats:italic> to establish H2AK119ub. CBX8 depletion reduced the enrichment of H2AK119ub on <jats:italic>CDKN2C<\/jats:italic> and <jats:italic>SCEL<\/jats:italic> promoters. Moreover, depletion of CDKN2C and SCEL restored the repressed growth and invasion ability of LUAD cells caused by CBX8 knockdown. These findings demonstrate that CBX8 promotes LUAD growth and metastasis through the transcriptional repression of <jats:italic>CDKN2C<\/jats:italic> and <jats:italic>SCEL<\/jats:italic>. Our study uncovers the oncogenic role of CBX8 in LUAD progression and provides a new target for the diagnosis and therapy of LUAD.<\/jats:p>","DOI":"10.1002\/jcp.31124","type":"journal-article","created":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T17:34:47Z","timestamp":1695317687000},"page":"2710-2723","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["CBX8 promotes lung adenocarcinoma growth and metastasis through transcriptional repression of CDKN2C and SCEL"],"prefix":"10.1002","volume":"238","author":[{"given":"Hao","family":"Chen","sequence":"first","affiliation":[{"name":"Haihe Laboratory of Cell Ecosystem, College of Life Sciences Nankai University Tianjin China"},{"name":"Department of Biochemistry and Molecular Biology The Province and Ministry Co\u2010sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University Tianjin 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