STAT3-induced upregulation of lncRNA MEG3 regulates the growth of cardiac hypertrophy through miR-361-5p/HDAC9 axis

Sci Rep. 2019 Jan 24;9(1):460. doi: 10.1038/s41598-018-36369-1.


Cardiac hypertrophy is closely correlated with diverse cardiovascular diseases, augmenting the risk of heart failure and sudden death. Long non-coding RNAs (lncRNAs) have been studied in cardiac hypertrophy for their regulatory function. LncRNA MEG3 has been reported in human cancers. Whereas, it is unknown whether MEG3 regulates the growth of cardiac hypertrophy. Therefore, this study aims to investigate the specific role of MEG3 in the progression of cardiac hypertrophy. Here, we found that MEG3 contributed to the pathogenesis of cardiac hypertrophy. MEG3 expression was remarkably strengthened in the mice heart which undergone the transverse aortic constriction (TAC). Moreover, qRT-PCR analysis revealed that MEG3 was upregulated in the cardiomyocytes which were treated with Ang-II. Silenced MEG3 inhibited the increasing size of hypertrophic cardiomyocytes and reversed other hypertrophic responses. Mechanically, MEG3 could affect cardiac hypertrophy by regulating gene expression. Mechanically, we found that MEG3 could be upregulated by the transcription factor STAT3 and could regulate miR-361-5p and HDAC9 by acting as a ceRNA. Finally, rescue assays were made to do further confirmation. All our findings revealed that STAT3-inducetd upregulation of lncRNA MEG3 controls cardiac hypertrophy by regulating miR-362-5p/HDAC9 axis.

MeSH terms

  • Animals
  • Binding Sites
  • Cardiomegaly / genetics*
  • Cardiomegaly / metabolism*
  • Cardiomegaly / pathology
  • Gene Expression Regulation*
  • Histone Deacetylases / genetics*
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Models, Biological
  • Myocytes, Cardiac / metabolism
  • Nucleotide Motifs
  • Position-Specific Scoring Matrices
  • Protein Binding
  • RNA Interference
  • RNA, Long Noncoding / genetics*
  • Repressor Proteins / genetics*
  • STAT3 Transcription Factor / metabolism*


  • MEG3 non-coding RNA, mouse
  • MIRN361 microRNA, mouse
  • MicroRNAs
  • RNA, Long Noncoding
  • Repressor Proteins
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Hdac9 protein, mouse
  • Histone Deacetylases