Dataset Information

Histone-fold centromere protein W (CENP-W) is associated with the biological behavior of hepatocellular carcinoma cells.

ABSTRACT: Centromere protein W (CENP-W), identified as a centromeric component, plays an important role in the cell life cycle. However, how CENPW expression affects biological processes in liver cancer cells remains unknown. In this article, we found that CENPW was overexpressed in liver cancer tissues. Low CENPW expression was correlated with a better prognosis in hepatocellular carcinoma (HCC) patients, compared to high CENPW expression. The results of qRT-PCR and western blot assay showed that CENPW was effectively knocked down in HCC cells using siRNA transfection. Cell proliferation, migration, and invasion were inhibited. Cell apoptosis rates were increased. The cells were arrested in the G2/M phase of the cell cycle. Subsequently, 127 differentially expressed genes (DEGs) were identified based on RNA-seq data. GO and KEGG enrichment and PPI network analysis were performed. The novel DEGs were found and mainly enriched in nucleosome assembly and the complement system. In summary, our study indicated that overexpression of CENPW implied unfavorable prognosis and CENPW might be the potential predictive biomarker in liver cancer. Downregulation of CENPW might inhibit the HCC developmentby regulating the expression of the molecules in nucleosomes and the complement system.

SUBMITTER: Zhou Z

PROVIDER: S-EPMC8291794 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundHepatocellular carcinoma (HCC) is one of the deadliest tumors. The majority of HCC is detected in the late stage, and the clinical results for HCC patients are poor. There is an urgent need to discover early diagnostic biomarkers and potential therapeutic targets for HCC.MethodsThe GSE87630 and GSE112790 datasets from the Gene Expression Omnibus (GEO) database were downloaded to analyze the differentially expressed genes (DEGs) between HCC and normal tissues. R packages were used for Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses of the DEGs. A Search Tool for Retrieval of Interacting Genes (STRING) database was used to develop a protein-protein interaction (PPI) network, and also cytoHubba, Molecular Complex Detection (MCODE), EMBL-EBI, CCLE, Gene Expression Profiling Interactive Analysis (GEPIA), and Oncomine analyses were performed to identify hub genes. Gene expression was verified with a third GEO dataset, GSE25097. The Cancer Genome Atlas (TCGA) database was used to explore the correlations between the hub genes and clinical indexes of HCC patients. The functions of the hub genes were enriched by gene set enrichment analysis (GSEA), and the biological significance of the hub genes was explored by real-time polymerase chain reaction (qRT-PCR), western blot, immunofluorescence, CCK-8, colony formation, Transwell and flow cytometry assays with loss-of-function experiments in vitro.ResultsCentromere protein N (CENPN) was screened as a hub gene affecting HCC tumorigenesis. Evaluation by Cox regression showed that a high level of CENPN expression was an independent danger variable for poor prognosis of HCC. GSEA showed that high CENPN expression was linked to the following pathways: liver cancer subclass proliferation, cell cycle, p53 signaling pathway, Rb1 pathway, positive regulation of cell cycle G1/S phase transition, and DNA damage response signal transduction by p53 class moderators. Further cell experiments showed that knocking down CENPN expression decreased the proliferation and colony-forming abilities of HepG2 and Huh7 cells as well as Ki67 expression in these cell lines. The cell cycle was arrested in G1 phase, which is consistent with previous experiments on CENPN downregulation., but neither migration nor invasion were significantly affected. Western blot results revealed that the expression of p53, p27, p21, CDK4, cyclin D1, CDK2, cyclin E, pRb, E2F1 and c-myc decreased after CENPN knockdown, but there was no significant change in total Rb levels. In addition, CENPN-knockdown cells subjected to irradiation showed significantly enhanced of γ-H2AX expression and reduced colony formation.ConclusionCENPN functions as an oncogene in HCC and may be a therapeutic target and promising prognostic marker for HCC.

Dataset Information

Histone-fold centromere protein W (CENP-W) is associated with the biological behavior of hepatocellular carcinoma cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets