CircAFF2 Promotes Neuronal Cell Injury in Intracerebral Hemorrhage by Regulating the miR-488/CLSTN3 Axis

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Intracerebral hemorrhage (ICH) is a severe stroke subtype with high mortality.
• Circular RNA AFF2 (circAFF2) levels are elevated in ICH patients, but its role is unclear.

Purpose of the Study:

• To investigate the mechanism of circAFF2 in ICH.
• To explore circAFF2 as a potential therapeutic target for ICH.

Main Methods:

• Established in vitro (hemin-treated neuronal cells) and in vivo (collagenase-induced ICH in mice) models.
• Quantified gene and protein expression (qRT-PCR, Western blotting).
• Validated molecular interactions (dual-luciferase, RNA-RIP) and assessed cellular/tissue injury.

Main Results:

• CircAFF2 expression was significantly upregulated in ICH models.
• CircAFF2 interacted with miR-488, and its knockdown/miR-488 overexpression reduced neuronal injury.
• CLSTN3 was identified as a miR-488 target; circAFF2 knockdown/miR-488 overexpression decreased CLSTN3 and protected cells.
• In vivo studies confirmed circAFF2 knockdown attenuated ICH via the miR-488/CLSTN3 pathway.

Conclusions:

• CircAFF2 promotes neuronal injury and exacerbates ICH by upregulating CLSTN3 through miR-488 sponging.
• CircAFF2 represents a potential therapeutic target for treating ICH.