LncRNA RP4-639F20.1 interacts with THRAP3 to attenuate atherosclerosis by regulating c-FOS in vascular smooth muscle

Ruyi Zhang1, Fan Bu2, Yubing Wang2

  • 1Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People's Republic of China.

Atherosclerosis
|August 7, 2023
PubMed
Abstract

Insights

Long noncoding RNA RP4-639F20.1 inhibits vascular smooth muscle cell proliferation and migration, protecting against atherosclerosis. This lncRNA RP4-639F20.1/THRAP3/c-FOS pathway offers potential therapeutic targets for atherosclerosis.

Area of Science:

  • Molecular Biology
  • Cardiovascular Research
  • Genetics

Background:

  • Aberrant vascular smooth muscle cell (VSMC) proliferation and migration are key in atherosclerosis (AS) pathogenesis.
  • Long noncoding RNAs (lncRNAs) regulate various diseases, but their role in VSMC function and AS is largely unknown.

Purpose of the Study:

  • To investigate the role of lncRNA RP4-639F20.1 in VSMC proliferation, migration, and AS development.
  • To elucidate the molecular mechanism underlying lncRNA RP4-639F20.1's function in AS.

Main Methods:

  • In vitro studies using VSMCs transfected with lncRNA RP4-639F20.1 overexpression or silencing vectors.
  • In vivo studies involving AAV9-mediated overexpression of lncRNA RP4-639F20.1 in ApoE-/- mice.
  • Analysis of molecular interactions using RNA fluorescence in situ hybridization, immunoprecipitation, and mRNA microarrays.

Main Results:

  • LncRNA RP4-639F20.1 interacts with THRAP3 and downregulates c-FOS, inhibiting VSMC proliferation and migration.
  • Overexpression of lncRNA RP4-639F20.1 reduced atherosclerosis and lipid levels in ApoE-/- mice.
  • Elevated c-FOS levels in coronary artery disease patients correlate with disease severity (SYNTAX score).

Conclusions:

  • The lncRNA RP4-639F20.1/THRAP3/c-FOS pathway suppresses VSMC proliferation and migration, offering protection against atherosclerosis.
  • LncRNA RP4-639F20.1 and c-FOS are potential therapeutic targets for treating atherosclerosis-related diseases.

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