# MicroRNA miR-188-5p enhances SUMO2/3 conjugation by targeting SENP3 and alleviates focal cerebral ischemia/reperfusion injury in rats

## TL;DR

This study shows that miR-188-5p reduces brain injury after stroke in rats by targeting SENP3 and increasing SUMO2/3 activity.

## Contribution

The study reveals a novel mechanism where miR-188-5p alleviates cerebral ischemia/reperfusion injury by enhancing SUMO2/3 conjugation through SENP3 suppression.

## Key findings

- miR-188-5p expression decreases in the brain after ischemia/reperfusion injury.
- miR-188-5p directly targets SENP3, reducing its levels and increasing SUMO2/3 conjugation.
- Inhibiting miR-188-5p worsens brain injury, while targeting SENP3 reverses this effect.

## Abstract

Expression of miR-188-5p changes upon experiencing cerebral I/R injury. SENP3 is a predicted target of miR-188-5p. The study aimed to examine the potential mechanism underlying the miR-188-5p mediated enhancement of SUMO2/3 conjugation via targeting SENP3 and alleviation against cerebral I/R injury.

Focal cerebral I/R was established in Sprague–Dawley rats using the MCAO model. The expression of miR-188-5p was modulated through intracerebroventricular (ICV) administration of its mimics or inhibitors. The expression of miR-188-5p, SENP3, and SUMO2/3 was detected using RT-qPCR or western blot analysis. Dual luciferase reporter assays were conducted to demonstrate the targeting effect of miR-188-5p on SENP3 in N2a cells. HE staining and TUNEL staining were performed to evaluate neurocellular morphological changes and detect neurocellular apoptosis, respectively. The extent of neurological deficits was evaluated using mNSS. TTC staining was used to evaluate the infarct area.

In the cerebral ischemic penumbra, the expression of miR-188-5p declined and SENP3 levels increased following I/R. Dual luciferase reporter assays confirmed that miR-188-5p directly acted on SENP3 in N2a cells. As a self-protective mechanism, SUMO2/3 conjugation increased after reperfusion. After ICV administration of miR-188-5p inhibitor, the expression of miR-188-5p was down-regulated, the expression of SENP3 was up-regulated, the SUMO2/3 conjugation decreased, and cerebral I/R injury was exacerbated. However, ICV administration of small hairpin RNA targeting SENP3 partially reversed the effects of the miR-188-5p inhibitor.

MiR-188-5p mitigated cerebral I/R injury by down-regulating SENP3 expression and consequently enhancing SUMO2/3 conjugation in rats.