Regulatory Mechanism miR-302a-3p/E2F1/SNHG3 Axis in Nerve Repair Post Cerebral Ischemic Stroke

Title:Regulatory Mechanism miR-302a-3p/E2F1/SNHG3 Axis in Nerve Repair Post Cerebral Ischemic Stroke

Volume: 18 Issue: 5

Author(s): Xiaoyu Sun, Lizhou Wang, Xueqing Huang, Shi Zhou*Tianpeng Jiang

Affiliation:

• Department of Interventional Radiology, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China

Keywords: Cerebral ischemic stroke, nerve repair, miR-302a-3p, transcription factor, E2F1, lncRNA SNHG3, brain injury, transcription activation.

Abstract:

Objective: Cerebral ischemic stroke (CIS) remains a primary cause of death worldwide. The current knowledge has identified the implication of microRNAs (miRNAs) in the pathophysiology of CIS. This study investigated the mechanism of miR-302a-3p in nerve repair post CIS.

Methods: A middle cerebral artery occlusion (MCAO) model was established in mice to simulate CIS. miR-302a-3p expression in brain tissues of MCAO mice was up-regulated by injecting agomiR-302a-3p. Neurological deficits of MCAO mice were evaluated through neurological function score, forelimb placing test, and balance beam walking test. Neuronal damage was measured using Nissl staining. The concentrations of nerve injury-related factors (S100B and GFAP) and the contents of neuroinflammatory factors (TNF-α and IL-1β) in serum were examined using ELISA kits. miR-302a-3p, E2F1, and long non-coding RNA (lncRNA) SNHG3 expressions in brain tissues of MCAO mice were determined using RT-qPCR and Western blot. The binding relationships between miR-302a-3p and E2F1 and E2F1 and SNHG3 were validated using dual-luciferase and ChIP assays, respectively.

Results: miR-302a-3p expression was reduced in brain tissues of MCAO mice. miR-302a-3p overexpression increased the number of neurons, decreased the concentrations of S100B and GFAP, reduced the contents of TNF-α and IL-1β, promoted nerve repair, and alleviated CIS-induced brain injury. miR-302a-3p targeted E2F1 expression, and E2F1 activated SNHG3 transcription. E2F1 overexpression or SNHG3 overexpression reversed the effect of miR-302a-3p overexpression on nerve repair in MCAO mice.

Conclusion: miR-302a-3p overexpression repressed SNHG3 transcription by targeting E2F1 expression, thereby promoting nerve repair and alleviating CIS.

Cite this article as:

Sun Xiaoyu , Wang Lizhou , Huang Xueqing, Zhou Shi*, Jiang Tianpeng , Regulatory Mechanism miR-302a-3p/E2F1/SNHG3 Axis in Nerve Repair Post Cerebral Ischemic Stroke, Current Neurovascular Research 2021; 18 (5) . https://dx.doi.org/10.2174/1567202618666211210155715