A novel role of Krüppel-like factor 8 as an apoptosis repressor in hepatocellular carcinoma.

摘要: Kruppel-like factor 8 (KLF8), a cancer-promoting that regulates critical gene transcription and cellular cancer-related events, has been implicated in tumor development progression. However, the functional role of KLF8 pathogenesis hepatocellular carcinoma (HCC) remains largely unknown. The expression patterns genome-wide regulatory profiles HCC cells after knockout were analyzed by using RNA sequencing (RNA-seq) chromatin immunoprecipitation (ChIP-seq) histone H3 lysine 27 acetylation (H3K27ac) combined with bioinformatics analysis. Transcription factor-binding motifs recognized evaluated motif For predicted target genes, transcriptional changes examined ChIP, loss function experiments conducted siRNA transfection. functioned as repressor mainly regulated apoptotic-related genes directly. A total 1,816 differentially expressed identified significantly corresponded to global H3K27ac status. Furthermore, two high-mobility group AT-hook 2 (HMGA2) matrix metalloproteinase 7 (MMP7), important participants KLF8-mediated anti-apoptotic effect HCC. Knockout enhanced cell apoptosis process caused increase associated H3K27ac, whereas suppression HMGA2 or MMP7 attenuated these biological effects. Our work suggests novel mechanism for regulation facilitates discovery potential therapeutic targets treatment.