GATA2 promotes hepatitis B virus-associated hepatocellular carcinoma development by regulating AURKA.

Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) refers to liver cancer caused by chronic HBV infection and is the leading cause of liver cancer globally. Although aurora kinase A (AURKA) has been reported to be highly expressed in HBV-associated HCC, its specific mechanisms of action remain unclear. Through bioinformatics analysis (Gene Expression Omnibus (GEO)) and experimental validation (Western blot), the expression levels of AURKA, hepatitis B virus X protein (HBX), and GATA binding protein 2 (GATA2) were assessed. A HepG2.2.15 cell model was established. Functional assays (colony formation, flow cytometry, mouse xenograft tumor model) and mechanistic studies (dual-luciferase reporter assay, JASPAR database analysis, and chromatin immunoprecipitation (ChIP)) were conducted to investigate the mechanism of AURKA in HBV-associated HCC. Bioinformatics analysis identified AURKA as a core gene in HBV- associated HCC. AURKA was highly expressed in HBV-associated HCC. Knockdown of AURKA inhibited the proliferation of HepG2.2.15 cells, induced apoptosis, and reduced the protein level of the autophagy substrate P62 as well as the ratio of the autophagy marker LC3BII/LC3BI. By forming a complex with GATA2, HBX enhanced the transcriptional activity of the AURKA promoter, thereby promoting the malignant phenotypes of HepG2.2.15 cells. Additionally, in vivo experiments demonstrated that knockdown of GATA2 inhibited tumor growth. In conclusion, GATA2-regulated AURKA promotes the development of HBV-associated HCC, underscoring its potential as a therapeutic target.