title: Epigenetic regulation of microRNA-128a expression contributes to the apoptosis-resistance of human T-cell leukaemia jurkat cells by modulating expression of fas-associated protein with death domain (FADD).
abstract: Increased expression of miR-128a is often observed in acute lymphoblastic leukaemia (ALL) compared with its expression in acute myeloid leukaemia (AML). The objective of this study was to investigate the role of miR-128a, especially that in the Fas-signalling pathway, in T-cell leukaemia cells. The role of miR-128a in Fas-mediated apoptosis was examined by using Fas-activating antibody (CH-11)-susceptible Jurkat cells and -resistant Jurkat/R cells. Whereas ectopic expression of miR-128a conferred Fas-resistance on Jurkat cells by directly targeting Fas-associated protein with death domain (FADD), antagonizing miR-128a expression sensitized Jurkat/R cells to the Fas-mediated apoptosis through derepression of FADD expression. Myeloid leukaemia HL60 and K562 cells were also CH-11-resistant, sharing a similar resistant mechanism with Jurkat/R cells. Furthermore, CH-11 induced demethylation of the promoter region of miR-128a with resultant up-regulation of miR-128a expression in Jurkat/R cells, which was shown to be a mechanism for the resistance ofJurkat/R cells to Fas-mediated apoptosis. Our results indicate that the induction of miR-128a expression by DNA demethylation is a novel mechanism of resistance to Fas-mediated apoptosis.
authors: Nami
authors: N
authors: Yamada
authors: Shunsuke
authors: S
authors: Noguchi
authors: Minami
authors: M
authors: Kumazaki
authors: Haruka
authors: H
authors: Shinohara
authors: Kohei
authors: K
authors: Miki
authors: Tomoki
authors: T
authors: Naoe
authors: Yukihiro
authors: Y
authors: Akao
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D053200:Fas-Associated Death Domain Protein / Q000096:biosynthesis / Q000235:genetics*; D015870:Gene Expression; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D015458:Leukemia, T-Cell / Q000235:genetics* / Q000473:pathology*; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D015854:Up-Regulation; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C505533:FADD protein, human; C491901:FAS protein, human; D053200:Fas-Associated Death Domain Protein; C545189:MIRN128 microRNA, human; D035683:MicroRNAs; D019014:fas Receptor