Circular RNA circ-RELL1 regulates inflammatory response by miR-6873-3p/MyD88/NF-κB axis in endothelial cells

Area of Science:

• Molecular Biology
• Cardiovascular Research
• Cell Biology

Background:

• Endothelial inflammation is a key factor in atherosclerotic cardiovascular disease (ASCVD) pathogenesis.
• The specific roles of circular RNAs (circRNAs) in endothelial inflammation remain largely unexplored.
• Oxidized low-density lipoprotein (ox-LDL) is implicated in triggering endothelial inflammatory responses.

Purpose of the Study:

• To investigate the role of circ-RELL1 in endothelial inflammation.
• To elucidate the underlying molecular mechanisms of circ-RELL1 in ox-LDL-induced endothelial cells.
• To identify potential therapeutic targets for ASCVD.

Main Methods:

• High-throughput circRNA microarray assays were used for initial identification.
• Knockdown of circ-RELL1 was performed to assess its functional impact.
• RNA-binding assays were employed to confirm direct interactions between circ-RELL1 and miR-6873-3p.
• Western blotting and other molecular techniques were used to analyze protein and pathway activation.

Main Results:

• circ-RELL1 was identified as a pro-inflammatory circRNA in ox-LDL-treated human umbilical vein endothelial cells (HUVECs).
• Knockdown of circ-RELL1 significantly reduced the expression of adhesion molecules ICAM1 and VCAM1.
• circ-RELL1 directly binds to miR-6873-3p, inhibiting its function and consequently promoting MyD88-mediated NF-κB activation.
• circ-RELL1 exacerbates inflammation by interfering with the inhibitory effect of miR-6873-3p on the MyD88/NF-κB pathway.

Conclusions:

• circ-RELL1 plays a pro-inflammatory role in endothelial cells stimulated by ox-LDL.
• A novel regulatory pathway involving circ-RELL1, miR-6873-3p, MyD88, and NF-κB activation in endothelial inflammation is described.
• circ-RELL1 represents a potential therapeutic target for managing endothelial inflammation in ASCVD.