Role of microRNA-143 in Fas-mediated apoptosis in human T-cell leukemia Jurkat cells.
Treatment of Jurkat T cells with Fas-activating antibody (CH-11) facilitated rapid cell death that was shown to be caspase-dependent apoptosis. The expression of miR-143 was up-regulated during the apoptosis with time. The increased expression of miR-143 emerged from 1 to 2h after the treatment, at which time the caspases-8 and -3 were also activated; and this increase was almost canceled by the pretreatment with an inhibitor of caspase-3 or -8. Furthermore, the transfection of Jurkat cells with mature miR-143 induced a significant growth suppression and enhancement of CH-11-induced apoptosis. On the contrary, an extracellular signal-regulated protein kinase 5 (ERK5), which was determined to be a target of miR-143 in colon cancer DLD-1 cells, was time-dependently down-regulated at the translational level after the treatment. During the apoptosis, the expression level of FasL was maintained and the level of nuclear-Foxo3a was increased in the early phase. These data suggest that the up-regulation of miR-143 could be related to the apoptosis in part by targeting ERK5, which leads to promotion of Foxo3a/FasL positive feedback loop.
Akao
Yukihiro
Y
Department of Medical Oncology, Gifu International Institute of Biotechnology, Kakamigahara, Gifu 504-0838, Japan. yakao@giib.or.jp
Nakagawa
Yoshihito
Y
Iio
Akio
A
Naoe
Tomoki
T
D000906:Antibodies / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D006801:Humans; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000473:pathology*; D035683:MicroRNAs / Q000502:physiology*; D048054:Mitogen-Activated Protein Kinase 7 / Q000235:genetics; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D000906:Antibodies; C481004:CH-11 anti-fas antibody, human; C542359:MIRN143 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D048054:Mitogen-Activated Protein Kinase 7