National Clinical Research Center for Infectious Diseases, The Third People’s Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen 518000, Guangdong, China.
School of Medicine, Southern University of Science and Technology, Shenzhen 518100, Guangdong, China.
Aging (Albany NY). 2023 Nov 17;15(22):12817-12851. doi: 10.18632/aging.205173.
Hepatocellular carcinoma (HCC) is a malignant tumor with a high prevalence and fatality rate. CBX2 has been demonstrated to impact the development and advancement of various cancers, albeit it has received limited attention in relation to HCC. In this study, CBX2 and CEP55 were screened out with the refined triple regulatory networks constructed by total RNA-seq datasets (TCGA-LIHC, GSE140845) and a robust prognostic model. Aberrantly higher expression levels of and in HCC may be caused by CNV alterations, promoter hypo-methylation, open chromatin accessibility, and greater active marks such as H3K4me3, H3K4me1, and H3K27ac. Functionally, , which was highly correlated with CD44, shaped a cancer stem cell-like phenotype by positively regulating cell-cycle progression, proliferation, invasion, metastasis, wound healing, and radiation resistance, revealed by combining bulk RNA-seq and scRNA-seq datasets. knockdown validated its role in affecting the cell cycle. Importantly, we revealed CBX2 could activate gene by cooperating with co-regulators or not rather than a recognizer of the repressive mark H3K27me3. For instance, we uncovered CBX2 bound to promoter of and to augment their expressions. showed a highly positive correlation with at pan-cancer level. In addition, and may enhance extracellular matrix reprograming via cancer-associated fibroblast. Surprisingly, patients with high expression of or exhibited a higher response to immunotherapy, indicating that and may be promising therapeutic targets for HCC patients.
肝细胞癌 (HCC) 是一种高发病率和高死亡率的恶性肿瘤。CBX2 已被证明会影响多种癌症的发展和进展，但在 HCC 方面的关注有限。在这项研究中，通过总 RNA-seq 数据集（TCGA-LIHC、GSE140845）和稳健的预后模型构建的精细化三重调控网络筛选出 CBX2 和 CEP55。HCC 中 和 的异常高表达可能是由于 CNV 改变、启动子低甲基化、开放染色质可及性以及更多的活性标记，如 H3K4me3、H3K4me1 和 H3K27ac 所致。功能上， 与 CD44 高度相关，通过正向调节细胞周期进程、增殖、侵袭、转移、伤口愈合和辐射抗性，塑造出类癌干细胞表型，这是通过结合批量 RNA-seq 和 scRNA-seq 数据集揭示的。 敲低验证了其在影响细胞周期中的作用。重要的是，我们揭示 CBX2 可以通过与共调节剂合作或不合作来激活基因，而不是识别抑制标记 H3K27me3 的识别器。例如，我们发现 CBX2 结合到 和 的启动子上，以增强它们的表达。 在泛癌水平上与 呈高度正相关。此外， 和 可能通过癌症相关成纤维细胞增强细胞外基质的重新编程。令人惊讶的是，高表达 或 的患者对免疫治疗的反应更高，表明 和 可能是 HCC 患者有前途的治疗靶点。
