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miR-330-3p alleviates the progression of atherosclerosis by downregulating AQP9

Erbo Shan1,2, Yuanyuan Yu2, Wenbo Tang3

  • 1The First Affiliated Hospital of Jinan University, Guangzhou, China.

Functional & Integrative Genomics
|March 6, 2023
PubMed

Insights

MicroRNA-330-3p (miR-330-3p) inhibits atherosclerosis (AS) by targeting aquaporin-9 (AQP9). This miR-330-3p/AQP9 pathway presents a potential new therapeutic target for AS treatment.

Area of Science:

  • Cardiovascular Biology
  • Molecular Biology
  • Biomedical Research

Background:

  • Atherosclerosis (AS) is a primary cause of cardiovascular diseases.
  • The specific role of aquaporin-9 (AQP9) in AS pathogenesis remains unclear.
  • Bioinformatics analysis suggested a regulatory link between miR-330-3p and AQP9 in AS.

Purpose of the Study:

  • To investigate the role of miR-330-3p and AQP9 in the development of atherosclerosis.
  • To elucidate the regulatory relationship between miR-330-3p and AQP9.
  • To explore the therapeutic potential of the miR-330-3p/AQP9 axis in AS.

Main Methods:

  • Atherosclerosis mouse models were established using ApoE-/- mice on a high-fat diet.
  • Histological analyses (H&E, Oil red O) assessed atherosclerotic lesions.
  • Cellular assays (CCK8, EdU, wound scratch, Transwell, flow cytometry) evaluated HUVEC proliferation, migration, invasion, apoptosis, and cell cycle.
  • Dual-luciferase reporter assay confirmed the direct interaction between miR-330-3p and AQP9.

Main Results:

  • AS mice exhibited decreased miR-330-3p expression and increased AQP9 expression.
  • Overexpression of miR-330-3p or AQP9 knockdown reduced ox-LDL-induced HUVEC apoptosis and promoted proliferation and migration.
  • Dual-luciferase assay confirmed that AQP9 is a direct target of miR-330-3p.

Conclusions:

  • miR-330-3p plays an inhibitory role in atherosclerosis by directly targeting and downregulating AQP9.
  • The miR-330-3p/AQP9 axis represents a novel molecular mechanism in AS.
  • Targeting the miR-330-3p/AQP9 pathway holds promise for future AS therapies.

Keywords:
AQP9AtherosclerosisCardiovascular diseasemiR-330-3p

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