title: Biphasic regulation of autophagy by miR-96 in prostate cancer cells under hypoxia.
abstract: Autophagy favors cell survival under hypoxia, and increasing evidence revealed that microRNAs regulate autophagy. We report here hypoxia increased the expression of miR-96 in prostate cancer cells, and miR-96 stimulated autophagy by suppressing MTOR. We found that inhibition of miR-96 abolished hypoxia-induced autophagy. Paradoxically, ectopic over-expression of miR-96 to a certain threshold, also abolished the hypoxia-induced autophagy. Further studies have shown that high levels of miR-96 inhibited autophagy through suppressing ATG7, a key autophagy-associated gene. Importantly, the miR-96 expression level threshold was determined, and the effects of miR-96 on autophagy on either side of the threshold were opposite. These data demonstrate hypoxia-induced autophagy is at least partially regulated by miR-96; miR-96 can promote or inhibit autophagy by principally inhibiting MTOR or ATG7 depending on the expression levels of miR-96. Our observation might reveal a novel regulatory mode of autophagy by microRNAs under hypoxia.
authors.affiliation: Department of urology, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, China. Department of biobank, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of central laboratory, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Hao-Zheng
authors.initials: HZ
authors.lastname: Yang
authors.affiliation: Department of urology, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Bai-Jun
authors.initials: BJ
authors.lastname: Dong
authors.affiliation: Department of central laboratory, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Han-Bing
authors.initials: HB
authors.lastname: Zou
authors.affiliation: Department of central laboratory, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of biobank, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Xian-Ming
authors.initials: XM
authors.lastname: Kong
authors.affiliation: Department of urology, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Yi-Ran
authors.initials: YR
authors.lastname: Huang
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics; D000071193:Autophagy-Related Protein 7; D015687:Cell Hypoxia / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D044764:Ubiquitin-Activating Enzymes / Q000037:antagonists & inhibitors*
chemical_list: C541492:MIRN96 microRNA, human; D035683:MicroRNAs; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes