title: MiR-129 triggers autophagic flux by regulating a novel Notch-1/ E2F7/Beclin-1 axis to impair the viability of human malignant glioma cells.
abstract: Abnormalities of autophagy have been implicated in an increasing number of human cancers, including glioma. To date, there is a wealth of evidence indicating that microRNAs (miRNAs) contribute significantly to autophagy in a variety of cancers. Previous studies have suggested that miR-129 functioned as an important inhibitor of the cell cycle and could promote the apoptosis of many cancer cell lines in vitro. Here, we reported that miR-129 acted as a potent inducer of autophagy. Forced expression of miR-129 could induce autophagic flux by targetedly suppressing Notch-1 in glioma cells. The autophagy induced by miR-129 could restrain the activity of mammalian target of rapamycin (mTOR) and upregulate Beclin-1. Moreover, we demonstrated that E2F transcription factor 7 (E2F7) could also trigger autophagic flux by upregulating Beclin-1 and mediating miR-129-induced autophagy. Additionally, knockdown of Notch-1 could upregulate the expression of E2F7, whereas downregulation of E2F7 alleviated shNotch-1-induced autophagic flux. In particular, knockdown of endogenous Beclin-1 could effectively reduce autophagic flux stimulated by miR-129 and E2F7. Interestingly, upon attenuation of miR-129- or E2F7-triggered autophagic flux rescued cell viability suppressed by them. More importantly, intratumoral injection of pHAGE-miR-129 lentivirus in a nude mouse xenograft model significantly restrained tumor growth and triggered autophagy. In conclusion, these findings identify a new function for miR-129 as a potent inducer of autophagy through a novel Notch-1/E2F7/Beclin-1 axis in glioma.
authors.affiliation: School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Neurosurgery, Wuhan University Renmin Hospital, Wuhan 430060, China.
authors.forename: Haiwei
authors.initials: H
authors.lastname: Lian
authors.affiliation: School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
authors.forename: Huilin
authors.initials: H
authors.lastname: Tu
authors.affiliation: School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
authors.forename: Song
authors.initials: S
authors.lastname: Han
authors.affiliation: School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yin
authors.affiliation: School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.|Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China.
authors.forename: Biwen
authors.initials: B
authors.lastname: Peng
authors.affiliation: Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A & M University, Texas 77843, USA.
authors.forename: Beiyan
authors.initials: B
authors.lastname: Zhou
authors.affiliation: School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.|Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: He
authors.affiliation: School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.|Hubei Province Key Laboratory of Allergy and Immunology, Wuhan 430071, China.
authors.forename: Wanhong
authors.initials: W
authors.lastname: Liu
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics*; D000071186:Beclin-1 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D050702:E2F7 Transcription Factor / Q000378:metabolism*; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009368:Neoplasm Transplantation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D014183:Transplantation, Heterologous; D015854:Up-Regulation
chemical_list: C491997:BECN1 protein, human; D000071186:Beclin-1; D050702:E2F7 Transcription Factor; C481054:E2F7 protein, human; D035683:MicroRNAs; C541915:Mirn129 microRNA, human; C497761:NOTCH1 protein, human; D034741:RNA, Small Interfering; D051881:Receptor, Notch1; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: E2F7; Notch-1; autophagy; glioma; miR-129
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