DNA hypermethylation of aurora kinase A in hepatitis C virus‑positive hepatocellular carcinoma.

Abstract	Changes in the methylation levels of tumor suppressor genes or proto‑oncogenes are involved in the pathogenesis of hepatitis C virus (HCV) infection‑induced hepatocellular carcinoma (HCC). The aim of the present study was to identify novel aberrantly methylated differentially expressed genes by integrating mRNA expression proﬁle (GSE19665 and GSE62232) and methylation proﬁle (GSE60753) microarrays downloaded from the Gene Expression Omnibus database. Functional enrichment analysis of screened genes was performed using the DAVID software and BinGO database. Protein‑protein interaction (PPI) networks were constructed using the STRING database, followed by module analysis with MCODE software. The transcriptional and translational expression levels of crucial genes were confirmed using The Cancer Genome Atlas (TCGA) datasets and Human Protein Atlas database (HPA). A total of 122 downregulated/hypermethylated genes and 63 upregulated/hypomethylated genes were identiﬁed. These genes were enriched in the Gene Ontology biological processes terms of 'inflammatory response' [Fos proto‑oncogene, AP‑1 transcription factor subunit (FOS)] and 'cell cycle process' [aurora kinase A (AURKA), cyclin dependent kinase inhibitor 3 (CDKN3) and ubiquitin conjugating enzyme E2 C (UBE2C)]. PPI network and module analysis indicated that human oncogenes FOS, AURKA, CDKN3 and UBE2C may be hub genes. mRNA, protein expression and methylation levels of AURKA and FOS were validated by TCGA and HPA data. In conclusion, aberrantly methylated AURKA and FOS may be potential therapeutic targets for HCV‑positive HCC.
Authors	Zuohong Ma, Yefu Liu, Zhiqiang Hao, Xiangdong Hua, Wenxin Li
Journal	Molecular medicine reports (Mol Med Rep) Vol. 20 Issue 3 Pg. 2519-2532 (Sep 2019) ISSN: 1791-3004 [Electronic] Greece
PMID	31322223 (Publication Type: Journal Article)
Chemical References	AURKA protein, human Aurora Kinase A
Topics	Aurora Kinase A (genetics) Carcinoma, Hepatocellular (genetics, virology) DNA Methylation Databases, Genetic Gene Expression Profiling Gene Expression Regulation, Neoplastic Gene Regulatory Networks Hepacivirus (isolation & purification) Hepatitis C (complications, genetics) Humans Liver Neoplasms (genetics, virology)

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