Elevated ASF1B Promotes Apoptosis in Gastric Tumour Cells Through the Bax/Bcl-2-p53 Pathway and is Related to a Good Prognosis

Abstract

Background: Previous studies have shown that ASF1B, a H3-H4 histone chaperone, plays a key role in cancer. However, the prognostic relevance and mechanism of ASF1B in patients with gastric cancer (GC) are not clear. Therefore, we explored the prognostic role of ASF1B in gastric cancer and explored its biological function. Methods: From the bioinformatics perspective, R software was used for prognostic correlation analysis, Gene Set Enrichment Analysis (GSEA) and Weighted Gene Coexpression Network Analysis (WGCNA) were used to screen related differential genes, and R software was used for Gene Oncology（GO）functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. In vitro, CCK-8 colorimetric assays and wound healing assays were used to evaluate the cell proliferation and migration abilities. The mechanism was investigated by western blot and cell functional assays. Results: Bioinformatics analysis showed that ASF1B was highly expressed in gastric cancer and that its expression was negatively correlated with T stage and prognosis. Cox regression analysis showed that ASF1B could be used as an independent prognostic factor in gastric cancer. The module genes were identified by WGCNA, and the genes related to ASF1B expression were identified by a PPI coexpression network construction. GO analysis showed enrichment in the terms positive regulation of cell cycle, DNA integrity checkpoint, regulation of double strand break repair, and signal transduction of p53; KEGG analysis showed enrichment in the p53 signalling pathway. GSEA showed that ASF1B was highly enriched in gene sets such as p53 signalling pathway, base excision repair, homologous recombination, and mismatch repair. TIMER analysis showed that the expression of ASF1B was closely related to the key genes of p53 apoptosis. In vitro experiments showed that ASF1B gene knockdown enhanced the proliferation and migration of gastric cancer cells and inhibited gastric cancer cell apoptosis by downregulating P53/Bax and upregulating the expression of the Bcl-2 protein. Conclusions: ASF1B may be an independent prognostic factor in gastric cancer. Downregulation of ASF1B promotes the proliferation and invasion of gastric tumour cells and is related to poor prognosis.