miR-376b controls starvation and mTOR inhibition-related autophagy by targeting ATG4C and BECN1
| Autor: | Devrim Gozuacik, Carlos le Sage, Kumsal Ayse Tekirdag, Reuven Agami, Gozde Korkmaz |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Sequestosome-1 Protein
Programmed cell death Molecular Sequence Data Autophagy-Related Proteins R Medicine (General) Biology BAG3 Response Elements Models Biological 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Autophagy Humans RNA Messenger Molecular Biology 3' Untranslated Regions PI3K/AKT/mTOR pathway 030304 developmental biology Adaptor Proteins Signal Transducing Sirolimus QP Physiology 0303 health sciences Oligoribonucleotides Base Sequence TOR Serine-Threonine Kinases Signal transducing adaptor protein Membrane Proteins Q Science (General) Cell Biology BECN1 QL Zoology 3. Good health Cell biology Gene Expression Regulation Neoplastic Cysteine Endopeptidases MicroRNAs RB Pathology Starvation 030220 oncology & carcinogenesis Proteolysis Beclin-1 Apoptosis Regulatory Proteins Intracellular |
| Zdroj: | Autophagy Scopus-Elsevier |
| ISSN: | 1554-8627 |
| DOI: | 10.4161/auto.8.2.18351 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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