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miR-376b controls starvation and mTOR inhibition-related autophagy by targeting ATG4C and BECN1

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Korkmaz, Gözde and Le Sage, Carlos and Tekirdağ, Kumsal Ayşe and Agami, Reuven and Gözüaçık, Devrim (2012) miR-376b controls starvation and mTOR inhibition-related autophagy by targeting ATG4C and BECN1. Autophagy, 8 (2). pp. 165-176. ISSN 1554-8627

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Official URL: http://dx.doi.org/10.4161/auto.8.2.18351

Abstract

Macroautophagy (autophagy) is the major intracellular degradation pathway for long-lived proteins and organelles. It helps the cell to survive a spectrum of stressful conditions including starvation, growth factor deprivation and misfolded protein accumulation. Moreover, abnormalities of autophagy play a role in major health problems including cancer and neurodegenerative diseases. Yet, mechanisms controlling autophagic activity are not fully understood. Here, we describe hsa-miR-376b (miR-376b) as a new microRNA (miRNA) regulating autophagy. We showed that miR-376b expression attenuated starvation- and rapamycin-induced autophagy in MCF-7 and Huh-7 cells. We discovered autophagy proteins ATG4C and BECN1 (Beclin 1) as cellular targets of miR-376b. Indeed, upon miRNA overexpression, both mRNA and protein levels of ATG4C and BECN1 were decreased. miR-376b target sequences were present in the 3' UTR of ATG4C and BECN1 mRNAs and introduction of mutations abolished their miR-376b responsiveness. Antagomir-mediated inactivation of the endogenous miR-376b led to an increase in ATG4C and BECN1 levels. Therefore, miR-376b controls autophagy by directly regulating intracellular levels of two key autophagy proteins, ATG4C and BECN1.

Item Type:Article
Additional Information:DG is the corresponding author
Uncontrolled Keywords:Macroautophagy, mammalian autophagy regulation, microRNA, hsa-miR-376b, Beclin1, Atg4C, drug research
Subjects:Q Science > Q Science (General)
R Medicine > R Medicine (General)
R Medicine > RB Pathology
Q Science > QL Zoology
Q Science > QP Physiology
ID Code:18952
Deposited By:Devrim Gözüaçık
Deposited On:06 Apr 2012 15:42
Last Modified:31 Jul 2019 09:22

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