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MiR-449a-5p mediates mitochondrial dysfunction and phenotypic transition by targeting Myc in pulmonary arterial

Chen Zhang1,2, Cui Ma2,3, Lixin Zhang2,3

  • 1College of Pharmacy, Harbin University of Commerce, Harbin, 150076, People's Republic of China.

Journal of Molecular Medicine (Berlin, Germany)
|February 5, 2019
PubMed

Insights

Downregulated miR-449a-5p contributes to pulmonary arterial hypertension (PAH) by impairing mitochondria and promoting smooth muscle cell proliferation via the Myc pathway.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Cellular Metabolism

Background:

  • Pulmonary arterial hypertension (PAH) involves complex molecular pathways in the pulmonary vasculature.
  • The role of microRNAs, particularly in energy metabolism and smooth muscle cell phenotype, remains incompletely understood in PAH.

Purpose of the Study:

  • To investigate the role of microRNAs in the pathogenesis of hypoxic pulmonary arterial hypertension (PAH).
  • To elucidate the function of miR-449a-5p in pulmonary arterial smooth muscle cell (PASMC) metabolism and phenotype.
  • To identify molecular targets and pathways regulated by miR-449a-5p in PAH.

Main Methods:

  • Genome-wide miRNA sequencing to identify dysregulated miRNAs in PAH.
  • Experimental validation of miR-449a-5p levels in hypoxic PAH and PASMCs.
  • Assessing the impact of miR-449a-5p on mitochondrial function and PASMC phenotype.
  • Investigating the regulatory relationship between miR-449a-5p and the transcription factor Myc.

Main Results:

  • miR-449a-5p was found to be downregulated in hypoxic PAH and PASMCs.
  • Reduced miR-449a-5p levels correlated with mitochondrial dysfunction and phenotypic changes in PASMCs.
  • miR-449a-5p negatively regulates the transcription factor Myc.
  • The miR-449a-5p/Myc axis drives PASMC proliferation and contributes to PAH pathology.

Conclusions:

  • The miR-449a-5p/Myc axis is a critical regulator in the development and progression of PAH.
  • Dysregulation of miR-449a-5p contributes to mitochondrial dysfunction and aberrant PASMC behavior in PAH.
  • Targeting the miR-449a-5p/Myc pathway offers potential therapeutic strategies for PAH.
Keywords:
MetabolismMiR-449a-5pMycPhenotypic transitionPulmonary arterial hypertension

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