title: Role of EZH2 in the growth of prostate cancer stem cells isolated from LNCaP cells.
abstract: Enhancer of zeste homolog 2 (EZH2) plays a crucial role in embryonic and somatic stem cells for their proliferation and differentiation. However, the roles and underlying mechanisms of EZH2 in prostate cancer stem cells (PCSCs) remain unknown. This study aimed to investigate the effects of EZH2 on PCSCs. PCSCs were isolated from the human prostate cancer cell line LNcap by fluorescence activated cell sorting (FACS). EZH2 expression was compared between PCSCs and non-PCSCs. The association between EZH2 function and PCSC growth was investigated using siRNA-mediated knock-down of EZH2. Cell growth was investigated by MTT, cell cycle and apoptosis of PCSCs were explored by flow cytometric analysis. Finally, the upstream pathway miRNA level was determined via a luciferase reporter assay, and the downstream pathway cycle regulators were examined via reverse transcriptase-polymerase chain reaction. The results showed that LNcap cell line comprised a greater proportion of CD44+/CD133+ cells by comparison to the PC-3 cell line. EZH2 was up-regulated in PCSCs compared with non-PCSCs. Silence of EZH2 inhibited cell growth and the cell cycle and promoted the progression of apoptosis. Furthermore, EZH2 was a direct target of miR-101 in PCSCs and EZH2's mRNA levels were inversely correlated with miR-101 expression and cyclin E2 (a cell-cycle regulator) was suppressed by siEZH2. In conclusion, EZH2 is essential for PCSC growth, partly through a negative regulation by miR-101 and positively regulating cyclin E2.
authors.affiliation: Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China. xkw2005@163.com.
authors.forename: Kuiqing
authors.initials: K
authors.lastname: Li
authors.forename: Cheng
authors.initials: C
authors.lastname: Liu
authors.forename: Bangfen
authors.initials: B
authors.lastname: Zhou
authors.forename: Liangkuan
authors.initials: L
authors.lastname: Bi
authors.forename: Hai
authors.initials: H
authors.lastname: Huang
authors.forename: Tianxin
authors.initials: T
authors.lastname: Lin
authors.forename: Kewei
authors.initials: K
authors.lastname: Xu
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D016213:Cyclins / Q000378:metabolism; D000071221:Enhancer of Zeste Homolog 2 Protein; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D010455:Peptides / Q000378:metabolism; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D034741:RNA, Small Interfering / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; C503688:CCNE2 protein, human; D016213:Cyclins; D006023:Glycoproteins; D018960:Hyaluronan Receptors; C534072:MIRN101 microRNA, human; D035683:MicroRNAs; C000606023:PROM1 protein, human; D010455:Peptides; D034741:RNA, Small Interfering; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2