{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["11"],"submitter":["Xu LF"],"pubmed_abstract":["Evidence suggests that histone modification disorders are involved in leukemia pathogenesis. We previously reported that LukS-PV, a component of Panton-Valentine leukocidin (PVL), has antileukemia activities that can induce differentiation, increase apoptosis, and inhibit proliferation of acute myeloid leukemia (AML) cells. Furthermore, LukS-PV inhibited hepatoma progression by regulating histone deacetylation, speculating that LukS-PV may exert antileukemia activity by targeting histone modification regulators. In this study, the results showed that LukS-PV induced apoptosis by downregulating the methyltransferase SET8 and its target histone H4 monomethylated at Lys 20 (H4K20me1). Furthermore, chromatin immunoprecipitation sequencing and polymerase chain reaction identified the kinase <i>PIK3CB</i> as a downstream target gene for apoptosis mediated by SET8/H4K20me1. Finally, our results indicated that LukS-PV induced apoptosis <i>via</i> the PIK3CB-AKT-FOXO1 signaling pathway by targeting SET8. This study indicates that SET8 downregulation is one of the mechanisms by which LukS-PV induces apoptosis in AML cells, suggesting that SET8 may be a potential therapeutic target for AML. Furthermore, LukS-PV may be a drug candidate for the treatment of AML that targets epigenetic modifications."],"journal":["Frontiers in oncology"],"pagination":["718791"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8565356"],"repository":["biostudies-literature"],"pubmed_title":["LukS-PV Induces Apoptosis <i>via</i> the SET8-H4K20me1-PIK3CB Axis in Human Acute Myeloid Leukemia Cells."],"pmcid":["PMC8565356"],"pubmed_authors":["Xu LF","Zhang SS","Shi L","Qiang P","Chang WJ","Dai YY","Mei Y","Ding PS","Song KD","Ma XL","Ma F"],"additional_accession":[]},"is_claimable":false,"name":"LukS-PV Induces Apoptosis <i>via</i> the SET8-H4K20me1-PIK3CB Axis in Human Acute Myeloid Leukemia Cells.","description":"Evidence suggests that histone modification disorders are involved in leukemia pathogenesis. We previously reported that LukS-PV, a component of Panton-Valentine leukocidin (PVL), has antileukemia activities that can induce differentiation, increase apoptosis, and inhibit proliferation of acute myeloid leukemia (AML) cells. Furthermore, LukS-PV inhibited hepatoma progression by regulating histone deacetylation, speculating that LukS-PV may exert antileukemia activity by targeting histone modification regulators. In this study, the results showed that LukS-PV induced apoptosis by downregulating the methyltransferase SET8 and its target histone H4 monomethylated at Lys 20 (H4K20me1). Furthermore, chromatin immunoprecipitation sequencing and polymerase chain reaction identified the kinase <i>PIK3CB</i> as a downstream target gene for apoptosis mediated by SET8/H4K20me1. Finally, our results indicated that LukS-PV induced apoptosis <i>via</i> the PIK3CB-AKT-FOXO1 signaling pathway by targeting SET8. This study indicates that SET8 downregulation is one of the mechanisms by which LukS-PV induces apoptosis in AML cells, suggesting that SET8 may be a potential therapeutic target for AML. Furthermore, LukS-PV may be a drug candidate for the treatment of AML that targets epigenetic modifications.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021","modification":"2024-11-20T07:33:53.519Z","creation":"2022-02-11T12:42:29.348Z"},"accession":"S-EPMC8565356","cross_references":{"pubmed":["34745943"],"doi":["10.3389/fonc.2021.718791"]}}