MicroRNA miR-۱۸۸-۵p enhances SUMO۲/۳ conjugation by targeting SENP۳ and alleviates focal cerebral ischemia/reperfusion injury in rats

Objective(s): Expression of miR-۱۸۸-۵p changes upon experiencing cerebral I/R injury. SENP۳ is a predicted target of miR-۱۸۸-۵p. The study aimed to examine the potential mechanism underlying the miR-۱۸۸-۵p mediated enhancement of SUMO۲/۳ conjugation via targeting SENP۳ and alleviation against cerebral I/R injury.Materials and Methods: Focal cerebral I/R was established in Sprague–Dawley rats using the MCAO model. The expression of miR-۱۸۸-۵p was modulated through intracerebroventricular (ICV) administration of its mimics or inhibitors. The expression of miR-۱۸۸-۵p, SENP۳, and SUMO۲/۳ was detected using RT-qPCR or western blot analysis. Dual luciferase reporter assays were conducted to demonstrate the targeting effect of miR-۱۸۸-۵p on SENP۳ in N۲a 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.Results: In the cerebral ischemic penumbra, the expression of miR-۱۸۸-۵p declined and SENP۳ levels increased following I/R. Dual luciferase reporter assays confirmed that miR-۱۸۸-۵p directly acted on SENP۳ in N۲a cells. As a self-protective mechanism, SUMO۲/۳ conjugation increased after reperfusion. After ICV administration of miR-۱۸۸-۵p inhibitor, the expression of miR-۱۸۸-۵p was down-regulated, the expression of SENP۳ was up-regulated, the SUMO۲/۳ conjugation decreased, and cerebral I/R injury was exacerbated. However, ICV administration of small hairpin RNA targeting SENP۳ partially reversed the effects of the miR-۱۸۸-۵p inhibitor.Conclusion: MiR-۱۸۸-۵p mitigated cerebral I/R injury by down-regulating SENP۳ expression and consequently enhancing SUMO۲/۳ conjugation in rats.

Keywords:

Conjugated SUMO۲/۳ , Ischemia/Reperfusion injury , Ischemic stroke , MiR-۱۸۸-۵p SENP۳