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

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