AUTHOR=Zhang Guangjian , Wang Qingdong , Su Daoqing , Xie Yingliang 

TITLE=Long Non-coding RNAMALAT1 Knockdown Alleviates Cerebral Ischemia/Reperfusion Injury of Rats Through Regulating the miR-375/PDE4D Axis

JOURNAL=Frontiers in Neurology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.578765

DOI=10.3389/fneur.2020.578765

ISSN=1664-2295

ABSTRACT=<p><bold>Objectives:</bold> Cerebral ischemic/reperfusion injury (CI/RI) is the clinical manifestation of cerebral ischemic stroke, which severely affects the health and life of the patients. We aimed to investigate the regulatory mechanism of long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on CI/RI in this study.</p><p><bold>Methods:</bold> The expression of lncRNA MALAT1 and miR-375 was detected by qRT-PCR. MTT was utilized to measure the viability of PC-12 cells. The levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), and reactive oxygen species (ROS) were detected by LDH assay, SOD assay, and ROS assay, respectively. The apoptosis rate of PC-12 cells was measured by flow cytometry analysis. Through enzyme-linked immunosorbent assay, the levels of NF-α, IL-1β, and IL-6 were determined. The interactions between miR-375 and MALAT1/PDE4D were predicted by Starbase/Targetscan software and verified by the dual-luciferase reporter assay. Western blot assay was performed to determine the protein expression of Bcl-2, Caspase-3, and PDE4D.</p><p><bold>Results:</bold> LncRNA MALAT1 expression was highly upregulated in the middle cerebral artery occlusion (MCAO)/reperfusion (R) model of rats. Both MALAT1 downregulation and miR-375 upregulation reversed the inhibitory effect of oxygen and glucose deprivation (OGD)/R on cell viability and the promoting effects on LDH level, cell apoptosis, and inflammatory factors levels. MALAT1 targeted miR-375, whereas miR-375 targeted PDE4D. Overexpression of miR-375 attenuated OGD/R-induced injury in PC-12 cells by targeting PDE4D. Both the low expression of miR-375 and high expression of PDE4D reversed the promoting effect of MALAT1 knockdown on SOD level and the inhibitory effects on ROS level, inflammatory factor levels, and cell apoptosis.</p><p><bold>Conclusion:</bold> Suppression of MALAT1 alleviates CI/RI of rats through regulating the miR-375/PDE4D axis. This study provides a possible therapeutic strategy for human CI/RI in clinic.</p>