MicroRNA miR-188-5p enhances SUMO2/3 conjugation by targeting SENP3 and alleviates focal cerebral ischemia/reperfusion injury in rats | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 5، دوره 27، شماره 10، دی 2024، صفحه 1260-1267 اصل مقاله (741.9 K) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2024.76165.16485 | ||
| نویسندگان | ||
| Haofei Liu1؛ Huailong Chen2؛ Xiangxiang Zhang3؛ Ruijiao Niu1؛ Fei Shi1؛ Mingshan Wang1؛ Rui Dong1؛ Yang Yuan* 1؛ Gaofeng Zhang* 1 | ||
| 1Department of Anesthesiology, The Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, Shandong, China | ||
| 2Department of Anesthesiology, Qingdao Eight People’s Hospital, Qingdao, Shandong, China | ||
| 3Graduate School of Dalian Medical University, Dalian, Liaoning, China | ||
| چکیده | ||
| Objective(s): 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. Materials and Methods: 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. Results: 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. Conclusion: MiR-188-5p mitigated cerebral I/R injury by down-regulating SENP3 expression and consequently enhancing SUMO2/3 conjugation in rats. | ||
| کلیدواژهها | ||
| Conjugated SUMO2/3؛ Ischemia/reperfusion injury؛ Ischemic stroke؛ MiR-188-5p SENP3 | ||
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