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LncRNA KCNQ1OT1 Participates in Ox-LDL-Induced Proliferation/Apoptosis Imbalance in Vascular Smooth Muscle Cells by

Kunsheng Li1, Hailong Cao1, Mingqiang Fan2

  • 1Department of Cardiothoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Gulou District, Nanjing 210008, China.

Journal of Stroke and Cerebrovascular Diseases : the Official Journal of National Stroke Association
|July 8, 2022
PubMed

Insights

Long non-coding RNA KCNQ1OT1 regulates vascular smooth muscle cell proliferation and apoptosis under oxidized low-density lipoprotein stimulation by interacting with miR-196a-5p and FOXO1.

Area of Science:

  • Molecular Biology
  • Cardiovascular Research
  • Cell Biology

Background:

  • Oxidized low-density lipoprotein (ox-LDL) is a key factor in atherosclerosis.
  • Vascular smooth muscle cells (VSMCs) play a critical role in the development of atherosclerosis.
  • Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cardiovascular diseases.

Purpose of the Study:

  • To investigate the function and regulatory mechanisms of lncRNA KCNQ1OT1 in VSMCs exposed to ox-LDL.
  • To elucidate the interaction between KCNQ1OT1, miR-196a-5p, and FOXO1 in the context of ox-LDL stimulation.
  • To analyze the potential of the KCNQ1OT1/miR-196a-5p/FOXO1 axis as a biomarker or therapeutic target for atherosclerosis.

Main Methods:

  • RNA sequencing to identify transcriptome changes in VSMCs treated with ox-LDL.
  • Quantitative real-time PCR (qRT-PCR) and Western blotting to assess expression levels of KCNQ1OT1, miR-196a-5p, and FOXO1.
  • RNA immunoprecipitation, RNA pull-down, and dual-luciferase reporter assays to confirm molecular interactions.
  • Cell Counting Kit-8 (CCK-8) and flow cytometry to evaluate cell proliferation and apoptosis.
  • Analysis of KCNQ1OT1 and miR-196a-5p levels in high-fat-fed mouse models and human atherosclerosis patient samples.

Main Results:

  • Ox-LDL treatment led to decreased expression of KCNQ1OT1 and FOXO1, and increased expression of miR-196a-5p in VSMCs.
  • KCNQ1OT1 acted as a competing endogenous RNA (ceRNA), positively regulating FOXO1 and negatively regulating miR-196a-5p.
  • Modulation of the KCNQ1OT1/miR-196a-5p/FOXO1 pathway altered the proliferation/apoptosis imbalance in VSMCs under ox-LDL stimulation.
  • Elevated KCNQ1OT1 and reduced miR-196a-5p levels were observed in high-fat-fed mice and patients with carotid atherosclerosis.

Conclusions:

  • The KCNQ1OT1/miR-196a-5p/FOXO1 pathway is aberrantly expressed and mediates ox-LDL-induced proliferation/apoptosis imbalance in VSMCs.
  • This pathway represents a potential mechanism underlying ox-LDL-induced vascular dysfunction and atherosclerosis.
  • KCNQ1OT1 and miR-196a-5p may serve as potential diagnostic or prognostic biomarkers for atherosclerosis.
Keywords:
AtherosclerosisFOXO1lncRNAmicroRNAox-LDL

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