APF lncRNA regulates autophagy and myocardial infarction by targeting miR-188-3p

Nat Commun. 2015 Apr 10:6:6779. doi: 10.1038/ncomms7779.

Abstract

The abnormal autophagy is associated with a variety of cardiovascular diseases. Long noncoding RNAs (lncRNAs) are emerging as new factors in gene regulation, but how lncRNAs operate in the regulation of autophagy in the heart is unclear. Here we report that a long noncoding RNA, named autophagy promoting factor (APF), can regulate autophagic cell death by targeting miR-188-3p and ATG7. The results show that miR-188-3p suppresses autophagy and myocardial infarction by targeting ATG7. Further, we find that APF lncRNA regulates miR-188-3p, and thus affects ATG7 expression, autophagic cell death and myocardial infarction. Our present study reveals a novel regulating model of autophagic programme, which comprises APF, miR-188-3p and ATG7 in the heart. Modulation of their levels may serve as potential targets and diagnostic tools for novel therapeutic strategies of myocardial infarction and heart failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Autophagy / genetics*
  • Autophagy-Related Protein 7
  • Base Sequence
  • Gene Expression Regulation
  • Heart Failure / genetics*
  • Heart Failure / metabolism
  • Heart Failure / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Molecular Sequence Data
  • Myocardial Infarction / genetics*
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Oligonucleotides / genetics
  • Oligonucleotides / metabolism
  • Primary Cell Culture
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Signal Transduction

Substances

  • Atg7 protein, mouse
  • MIRN188 microRNA, mouse
  • MicroRNAs
  • Microtubule-Associated Proteins
  • Oligonucleotides
  • RNA, Long Noncoding
  • Autophagy-Related Protein 7