microRNA let-7c is essential for the anisomycin-elicited apoptosis in Jurkat T cells by linking JNK1/2 to AP-1/STAT1/STAT3 signaling

Published on Apr 18, 2016in Scientific Reports3.998
· DOI :10.1038/SREP24434
Zhiwei Zhou2
Estimated H-index: 2
Xijian Lu2
Estimated H-index: 2
+ 3 AuthorsFeiyue Xing12
Estimated H-index: 12
(JNU: Jinan University)
Anisomycin, an antibiotic produced by Streptomyces griseolus, strongly induces apoptosis in various tumor cells in vitro, superior dramatically to adriamycin. The present study aims to elucidate its detailed mechanistic process. The results showed that anisomycin sufficiently promoted the apoptosis in human leukemic Jurkat T cells at a quite low dose. microRNA let-7c (let-7c) contributed to the anisomycin-induced apoptosis, which could be abrogated by the inactivation of JNK signaling. The let-7c over-expression and the addition of its mimics facilitated the activation of AP-1, STAT1 and Bim by linking JNK1/2 to AP-1/STAT1, but rather inhibited the activation of STAT3 and Bcl-xL by connecting JNK1/2 to STAT3, followed by the augmented apoptosis in the cells. The let-7c deficiency reduced the AP-1, STAT1 and Bim activities, and enhanced the STAT3 and Bcl-xL, alleviating the anisomycin-induced apoptosis. The knockdown of the bim gene repressed the anisomycin-boosted apoptosis through the attenuation of the active Bak and Bax. The findings indicate for the first time that miR let-7c is essential for the anisomycin-triggered apoptosis by linking JNK1/2 to AP-1/STAT1/STAT3/Bim/Bcl-xL/Bax/Bak signaling. This provides a novel insight into the mechanism by which anisomycin leads to the tumor cell apoptosis, potentially laying the foundations for its development and clinical application.
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