MicroRNA-29a-3p regulates abdominal aortic aneurysm development and progression via direct interaction with PTEN

J Cell Physiol. 2020 Dec;235(12):9414-9423. doi: 10.1002/jcp.29746. Epub 2020 May 7.

Abstract

Various research studies have been conducted in deducing the role of microRNAs (miRNAs) in the pathogenesis and physiological processes of various systematic diseases. This study aims at demonstration of the important role played by miR-29a-3p, through association with phosphatase and tensin homolog (PTEN), in the regulation of abdominal aortic aneurysm development and progression. Quantitative real-time polymerase chain reaction (RT-qPCR) examined miRNA-19a-3p and PMEPA1 expression in multiplied vascular smooth muscle cells (VSMCs). Cell transfection upregulated or downregulated the genes and cell counting kit-8 assay determined cellular viability. RT-qPCR detected cellular proliferation and cell death using the cell proliferation and apoptosis biomarkers Ki87 and proliferating cell nuclear antigen, caspase-8 and caspase-3, respectively. Furthermore, luciferase assay analyzed the luciferase activity and western blot analysis determined miRNA-19a-3p and PMEPA1 protein expression in proliferation and apoptosis biomarkers. TargetScan 4.2 online software (www.targetscan.org) was used to perform the bioinformatics analysis so as to forecast the putative targets of miR-29a-3p and PTEN. The results inferred that there was an increased expression of miRNA-29a-3p found in AAA-mimic cells with increased cellular viability and significant pathological apoptosis. Further, when the expression of miRNA-29a-3p was downregulated, it reduced the cell viability of AAA cells. On the basis of the gene interplays, it can be understood that the PTEN was directly targeted by miRNA-29a-3p so as to regulate the AAA progression. Thus, PTEN was found to strengthen the proliferation effect of miRNA-29a-3p in AAA cells. The current study thus shed more insights about the molecular mechanistic roles of miRNA-29a-3p and PTEN, opening doors for novel therapeutic approach to AAA.

Keywords: PTEN; abdominal aortic aneurysm; apoptosis; microRNA-29a-3p.

MeSH terms

  • Aortic Aneurysm, Abdominal / genetics*
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Proliferation / genetics*
  • Cell Survival / physiology
  • Humans
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • MicroRNAs / genetics*
  • Myocytes, Smooth Muscle / metabolism
  • Signal Transduction / genetics
  • Up-Regulation

Substances

  • MIRN29a microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • PMEPA1 protein, human