Journal
AUTOPHAGY
Volume 8, Issue 2, Pages 165-176Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/auto.8.2.18351
Keywords
macroautophagy; mammalian autophagy regulation; microRNA; hsa-miR-376b; BECN1; Beclin 1; ATG4C; drug research
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Funding
- The Scientific and Technological Research Council of Turkey (TUBITAK) [107T153]
- EMBO Strategical Development and Installations Grant (EMBO-SDIG) [1449]
- Turkish Academy of Sciences (TUBA) GEBIP
- TUBITAK-BIDEB
- Sabanci University
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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.
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