MiR-129 triggers autophagic flux by regulating a novel Notch-1/ E2F7/Beclin-1 axis to impair the viability of human malignant glioma cells
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Xiong Chen1,*, Yingying Zhang1,*, Yingying Shi1, Haiwei Lian4, Huilin Tu1, Song Han1, Jun Yin1, Biwen Peng1,2, Beiyan Zhou5, Xiaohua He1,2, Wanhong Liu1,3
1School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China
2Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China
3Hubei Province Key Laboratory of Allergy and Immunology, Wuhan 430071, China
4Department of Neurosurgery, Wuhan University Renmin Hospital, Wuhan 430060, China
5Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A & M University, Texas 77843, USA
*These authors contributed equally to this work
Xiaohua He, e-mail: email@example.com
Wanhong Liu, e-mail: firstname.lastname@example.org
Keywords: miR-129, E2F7, Notch-1, autophagy, glioma
Received: July 07, 2015 Accepted: January 01, 2016 Published: January 25, 2016
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.
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