The interaction between 30b-5p miRNA and MBNL1 mRNA is involved in vascular smooth muscle cell differentiation in patients with coronary atherosclerosis

Int J Mol Sci. 2019 Dec 18;21(1):11. doi: 10.3390/ijms21010011.

Abstract

Vascular smooth muscle cells (VSMCs) in the arterial wall have diverse functions. In pathological states, the interplay between transcripts and microRNAs (miRNAs) leads to phenotypic changes. Understanding the regulatory role of miRNAs and their target genes may reveal how VSMCs modulate the pathogenesis of coronary artery disease. Laser capture microdissection was performed on aortic wall tissues obtained from coronary artery bypass graft patients with and without recent acute myocardial infarction (MI). The mSMRT-qPCR miRNA assay platform (MiRXES, Singapore) was used to profile miRNA. The miRNA data were co-analyzed with significant mRNA transcripts. TargetScan 7.1 was applied to evaluate miRNA-mRNA interactions. The miRNA profiles of 29 patients (16 MI and 13 non-MI) were evaluated. Thirteen VSMC-related miRNAs were differentially expressed between the MI and non-MI groups. Analysis revealed seven miRNA-targeted mRNAs related to muscular tissue differentiation and proliferation. TargetScan revealed that among the VSMC-related transcripts, MBNL1 had a recognition site that matched the hsa-miR-30b-5p target seed sequence. In addition to predicted analysis, our experiment in vitro with human VSMC culture confirmed that hsa-miR-30b-5p negatively correlated with MBNL1. Our data showed that overexpression of hsa-miR-30b-5p led to downregulation of MBNL1 in VSMCs. This process influences VSMC proliferation and might be involved in VSMC differentiation.

Keywords: aortic wall; atherosclerosis; microRNA; muscle cell differentiation; vascular smooth muscle cells.

MeSH terms

  • Aged
  • Cell Differentiation / genetics*
  • Comorbidity
  • Coronary Artery Disease / etiology*
  • Coronary Artery Disease / metabolism
  • Coronary Artery Disease / pathology
  • Disease Susceptibility
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Muscle, Smooth, Vascular / cytology*
  • Myocytes, Smooth Muscle / metabolism*
  • RNA Interference*
  • RNA-Binding Proteins / genetics*

Substances

  • MBNL1 protein, human
  • MIRN30b microRNA, human
  • MicroRNAs
  • RNA-Binding Proteins