title: microRNA let-7c is essential for the anisomycin-elicited apoptosis in Jurkat T cells by linking JNK1/2 to AP-1/STAT1/STAT3 signaling.
abstract: 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.
authors.affiliation: Institute of Tissue Transplantation and Immunology, Department of Immunobiology, Jinan University, Guangzhou 510632, China.|Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Jinan University, Guangzhou 510632, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Institute of Tissue Transplantation and Immunology, Department of Immunobiology, Jinan University, Guangzhou 510632, China.
authors.forename: Xijian
authors.initials: X
authors.lastname: Lu
authors.affiliation: Institute of Tissue Transplantation and Immunology, Department of Immunobiology, Jinan University, Guangzhou 510632, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Tissue Transplantation and Immunology, Department of Immunobiology, Jinan University, Guangzhou 510632, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Stomatology, Jinan University, Guangzhou 510632, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Tissue Transplantation and Immunology, Department of Immunobiology, Jinan University, Guangzhou 510632, China.|Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Jinan University, Guangzhou 510632, China.
authors.forename: Feiyue
authors.initials: F
authors.lastname: Xing
mesh_terms: D000841:Anisomycin / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019169:Jurkat Cells; D035683:MicroRNAs / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D035683:MicroRNAs; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; D018808:Transcription Factor AP-1; D051020:bcl-X Protein; C487931:mirnlet7 microRNA, human; D000841:Anisomycin; D048031:JNK Mitogen-Activated Protein Kinases