Ox-LDL-Induced Vascular Smooth Muscle Cell Dysfunction Partly Depends on the Circ_0044073/miR-377-3p/AURKA Axis in

Qiang Wang1, Tao Wang1, Siyuan Liang1

  • 1Department of Vascular Surgery, Taizhou University Affiliated Municipal Hospital.

Insights

Circular RNA hsa_circ_0044073 (circ_0044073) promotes atherosclerosis by sponging miR-377-3p, leading to increased AURKA expression. Inhibiting circ_0044073 may offer a therapeutic strategy for atherosclerosis.

Area of Science:

  • Cardiovascular Biology
  • Molecular Biology
  • RNA Biology

Background:

  • Atherosclerosis (AS) is a primary cause of cardiovascular diseases.
  • Circular RNA hsa_circ_0044073 (circ_0044073) is implicated in AS progression, but its regulatory mechanism is not fully understood.

Purpose of the Study:

  • To elucidate the specific regulatory mechanism of circ_0044073 in AS progression.
  • To investigate the role of circ_0044073 in oxidized low-density lipoprotein (Ox-LDL)-induced human vascular smooth muscle cell (VSMC) dysfunction.

Main Methods:

  • Utilized Ox-LDL-stimulated human VSMCs as an AS cell model.
  • Assessed circ_0044073 expression via RT-qPCR.
  • Evaluated cell viability, proliferation, migration, and invasion using MTT, EDU, colony formation, and Transwell assays.
  • Determined protein levels via Western blotting.
  • Validated regulatory mechanisms using bioinformatics, dual-luciferase reporter, and RNA pull-down assays.

Main Results:

  • Circ_0044073 expression was significantly elevated in AS patient serum and Ox-LDL-stimulated VSMCs.
  • Circ_0044073 acts as a sponge for miR-377-3p.
  • Knockdown of circ_0044073 or overexpression of miR-377-3p attenuated Ox-LDL-induced VSMC proliferation, migration, invasion, and inflammation.
  • AURKA was identified as a direct target of miR-377-3p, and circ_0044073 regulated AURKA expression via miR-377-3p adsorption.
  • Overexpression of AURKA partially reversed the inhibitory effects of circ_0044073 inhibition.

Conclusions:

  • Circ_0044073 promotes AS progression by upregulating AURKA expression through sponging miR-377-3p.
  • Circ_0044073 represents a potential therapeutic target for atherosclerosis.

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