Prognostic hub gene CBX2 drives a cancer stem cell-like phenotype in HCC revealed by multi-omics and multi-cohorts

Meng, Qingren1,2; Zhou, Qian3; Chen, Xi4; Chen, Jun1

2023-11-30

AGING-US   影响因子和分区

1945-4589

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 CBX2 and CEP55 in HCC may be caused by CNV alterations, promoter hypomethylation, open chromatin accessibility, and greater active marks such as H3K4me3, H3K4me1, and H3K27ac. Functionally, CBX2, 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. CBX2 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 CTNNB1 and CEP55 to augment their expressions. CBX2 showed a highly positive correlation with CEP55 at pan-cancer level. In addition, CBX2 and CEP55 may enhance extracellular matrix reprograming via cancer-associated fibroblast. Surprisingly, patients with high expression of CBX2 or CEP55 exhibited a higher response to immunotherapy, indicating that CBX2 and CEP55 may be promising therapeutic targets for HCC patients.

HCC CBX2 CEP55 regulatory network cell cycle

SCI

英语

第一 ; 通讯

Key medical disciplines in Shenzhen[SZXK076]

Cell Biology ; Geriatrics & Gerontology

Cell Biology ; Geriatrics & Gerontology

WOS:001117592100034

IMPACT JOURNALS LLC

Web of Science

1.Southern Univ Sci & Technol, Peoples Hosp Shenzhen 3, Natl Clin Res Ctr Infect Dis, Affiliated Hosp 2, Shenzhen 518000, Guangdong, Peoples R China
2.Southern Univ Sci & Technol, Sch Med, Shenzhen 518100, Guangdong, Peoples R China
3.Shenzhen Univ, Int Canc Ctr, Med Sch, Shenzhen 518100, Guangdong, Peoples R China
4.Southern Univ Sci & Technol, Sch Life Sci, Dept Biol, Shenzhen Key Lab Gene Regulat & Syst Biol, Shenzhen 518100, Guangdong, Peoples R China

Meng, Qingren,Zhou, Qian,Chen, Xi,et al. Prognostic hub gene CBX2 drives a cancer stem cell-like phenotype in HCC revealed by multi-omics and multi-cohorts[J]. AGING-US,2023,15(22).

Meng, Qingren,Zhou, Qian,Chen, Xi,&Chen, Jun.(2023).Prognostic hub gene CBX2 drives a cancer stem cell-like phenotype in HCC revealed by multi-omics and multi-cohorts.AGING-US,15(22).

Meng, Qingren,et al."Prognostic hub gene CBX2 drives a cancer stem cell-like phenotype in HCC revealed by multi-omics and multi-cohorts".AGING-US 15.22(2023).