title: Bortezomib induces apoptosis of endometrial cancer cells through microRNA-17-5p by targeting p21.
abstract: Bortezomib suppresses ubiquitin (Ub)-dependent protein degradation and preferentially kills various tumour cells in vitro and in animal models. However, its mechanism of action is not fully understood. We report that bortezomib inhibits the proliferation and proteasomal activity of human endometrial cancer cells and induces G2/M arrest and apoptosis by modulating the miRNA level. By miRNA microarray, iR-17-5p was the most downregulated of all those in HTB-111 and Ishikawa cells after bortezomib treatment. This observation was confirmed by quantitative real-time PCR (qRT-PCR). Target prediction using TargetScan software identified p21 as a potential target for miR-17-5p, which was confirmed by luciferase reporter, qRT-PCR and Western blot assays. The transfection of miR-17-5p mimics or siRNA-p21 reversed the effect of bortezomib on HTB-111 and Ishikawa cells, indicating that miR-17-5p may mediate the function of bortezomib by targeting p21 in endometrial cancer cells. These findings show novel mechanisms by which bortezomib inhibits proliferation and promotes the apoptosis of human endometrial cancer cells.
authors.affiliation: Gynecology and Obstetrics Department of the First Affiliated Hospital of JiNan University, Guangzhou, 510630, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Shen
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.forename: Jianping
authors.initials: J
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Meng
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Qing
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Bei
authors.initials: B
authors.lastname: Zhang
authors.forename: Haiyan
authors.initials: H
authors.lastname: Hu
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001483:Base Sequence; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D011719:Pyrazines / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D001897:Boronic Acids; D050759:Cyclin-Dependent Kinase Inhibitor p21; C524941:MIRN17 microRNA, human; D035683:MicroRNAs; D011719:Pyrazines; D034741:RNA, Small Interfering; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex
keywords: RNA interference (RNAi); apoptosis; cancer