多聚体组(PcG)蛋白的紊乱导致表观遗传基因沉默参与了肿瘤的发生。作为多聚体抑制性复合物1 (PRC1)的核心组分，染色体盒蛋白(CBX)识别H3K27me3以招募PRC1以维持抑制性转录状态。然而，这些CBX蛋白的个体生物学功能在肿瘤发生中是否具有深层次的影响的问题需要进一步研究。本研究使用癌症基因组图谱数据分析了多种癌症中CBX家族基因的mRNA表达，并发现五个CBX基因在不同类型的癌症中有不同的表达模式。这些分析结果与免疫组化结果一起表明，与邻近非肿瘤组织相比，CBX8在肺腺癌(LUAD)组织中的表达显著升高。过表达实验表明CBX8在体外促进LUAD细胞增殖和迁移。一致的是，CBX8敲除在细胞培养和小鼠模型中都减少了LUAD细胞的增殖和迁移。RNA测序结合实时RT-PCR分析揭示了CDKN2C和SCEL作为CBX8的靶基因。此外，染色质免疫沉淀实验证明CBX8直接结合到CDKN2C和SCEL启动子上以建立H2AK119ub。CBX8的消除减少了CDKN2C和SCEL启动子上H2AK119ub的富集。而CDKN2C和SCEL的消除恢复了CBX8敲除引起的LUAD细胞生长和侵袭能力受抑制的情况。这些发现表明，CBX8通过对CDKN2C和SCEL的转录抑制促进了LUAD的生长和转移。我们的研究揭示了CBX8在LUAD进展中的致癌作用，并为LUAD的诊断和治疗提供了新的靶点。© 2023 Wiley Periodicals LLC.

Dysregulation of polycomb group (PcG) proteins that mediate epigenetic gene silencing contributes to tumorigenesis. 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-depth 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-time RT-PCR assays revealed CDKN2C and SCEL as target genes of CBX8. Furthermore, chromatin immunoprecipitation assays indicated that CBX8 directly bound to the promoters of CDKN2C and SCEL to establish H2AK119ub. CBX8 depletion reduced the enrichment of H2AK119ub on CDKN2C and SCEL 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 CDKN2C and SCEL. Our study uncovers the oncogenic role of CBX8 in LUAD progression and provides a new target for the diagnosis and therapy of LUAD.© 2023 Wiley Periodicals LLC.