Luks-pv Induces Apoptosis Through Methyltransferase Set8 in Human Acute Myeloid Leukaemia Cells

Abstract

Background We previously reported that LukS-PV induces apoptosis in human acute myeloid leukaemia (AML) cells. Furthermore, SET8 is a member of the SET domain-containing methyltransferase family and overexpressed in numerous tumours, including AML and indicated a poor prognosis. However, it is unclear whether LukS-PV induce apoptosis via SET8. In current study, we aimed to investigate the regulatory mechanisms of SET8 and effects on AML cells under the LukS-PV.Methods Flow cytometry was performed to detect apoptosis in AML primary blasts/cell lines treated with LukS-PV and invasion of AML cells in vivo. The expression of SET8 was quantified through reverse-transcription PCR and western blotting. Chromatin-immunoprecipitation (ChIP) sequencing and bioinformatic methods was performed to explore transcriptional target genes which regulated by SET8-H4K20me1 axis. All experiments were performed in triplicate, and all statistical analyses were conducted using SPSS 16.0.Results In this research, we found that LukS-PV induce cell apoptosis in vitro and inhibit cell invasion in vivo. Our results further confirmed SET8 and H4K20me1 were downregulated in LukS-PV-treated AML cells. Furthermore, we confirmed that LukS-PV induced apoptosis via downregulating SET8/H4K20me1. Finally, Genome-wide analysis identified PIK3CB is the target gene for cell apoptosis mediated by SET8/H4K20me1. In a nutshell, LukS-PV induces apoptosis via the PIK3CB/PI3K/AKT/FOXO1 signal pathway by targeting SET8.Conclusions The present results indicate that LukS-PV induces apoptosis in AML cells by downregulating SET8 and regulating downstream molecular targets, suggesting that SET8 is a potential target for AML therapy using LukS-PV for anti-leukaemia treatment.