Inhibition of LncRNA MALAT1 Attenuates Cerebral Ischemic Reperfusion Injury via Regulating AQP4 Expression

Abstract

Stroke is one of the leading causes of mortality and disability worldwide. Long noncoding RNAs (lncRNAs) including MALAT1 have been shown to have critical roles in cerebral ischemia reperfusion injury (CIRI). However, the underlying mechanism of MALAT1 in CIRI has not been elucidated. The present study aimed to investigate the function and potential regulatory mechanism of MALAT1 in cerebral ischemic reperfusion injury. We established the middle cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation/reoxygenation (OGD/RX) model in vivo and in vitro, and then Cell Counting Kit-8 (CCK-8), RT-qPCR, flow cytometry analysis, lactate dehydrogenase (LDH) analysis, and 2,3,5-triphenyltetrazolium chloride (TTC) staining were used to examine cell viability, MALAT1, aquaporin-4 (AQP4) expression, LDH release, and infarct volume, respectively. The level of AQP4 was remarkably upregulated in CIRI 24 h/48 h or OGD/RX 24 h/48 h compared with the sham group. Knockdown of AQP4 could alleviate OGD/RX-induced injury through enhancing cell viability and reducing LDH release and the rate of apoptotic cells. Furthermore, we found that MALAT1 was also increased in OGD/RX 24 h/48 h and silencing of MALAT1 could decrease AQP4. Inhibition of MALAT1 could also protect OGD/RX-induced injury, while the protective effect of MALAT1 siRNA on cerebral ischemic reperfusion was disappeared after transfection with AQP4 plasmid, indicating that MALAT1 may play a protective role in brain stroke through regulating AQP4. Taken together, our study provides evidence that MALAT1 is involved in ischemic stroke by inhibiting AQP4. Therefore, MALAT1 may serve as a potential target for therapeutic intervention in ischemic brain injury.

Propofol protects cardiomyocytes from hypoxia/reoxygenation injury via regulating MALAT1/miR‐206/ATG3 axis

“…For instance, a recent animal study suggests that MALAT1 facilitates cerebral I/R injury by upregulating AQP4 expression. [33] Another study reports that, MALAT1 promotes the apoptosis of cardiomyocytes after myocardial infarction via repressing miR-144-3p. [34] MiR-206 has been reported to be a protective factor for cardiomyocytes: it protects cardiomyocytes against MIRI by inhibiting the expression of Gadd45β.…”

Upregulation of LncRNAs THRIL and Malat1 in Peripheral Blood of Ischemic Stroke Patients with Large Artery Atherosclerotic and Small Vessel Disease

“…The protective, anti-apoptotic, and anti-in ammatory roles of Malat1 in brain microvasculature and animal model were reported by Zhang et al in 2017 [50]. In another study has been demonstrated that Malat1 was signi cantly upregulated in vitro and in vivo models of IR/I and the inhibition of Malat1 could alleviate astrocyte cell injury, reduce brain injury and neurological behavior [13]. On the other hand, downregulation and the protective role of Malat1 in IS patients has been shown by Ren et.al in 2020 [37].…”

“…This is an RNA gene and its transcript has been con rmed as a non-coding RNA with a good diagnostic value in different types of human cancers [8]. Malat1 was rst identi ed in tumor tissue from patients with non-small cell lung cancer [9], and the relative upregulation of Malat1 has been associated with metastasis in lung, liver, and breast cancers [9,10], but also diabetes [11], angiogenesis [12] or animal models of cerebral ischemia [13]. Several studies demonstrated lncRNA Malat1 could promote in ammation [14][15][16][17], and coronary atherosclerosis disease (CAD) [18,19].…”

MELLT3 protects against cerebral ischemia-reperfusion (I/R) injury through up-regulation of m6A modification

“…Primary astrocyte culture MA-C (Mouse Astrocytes-cerebellar) were prepared from a post-natal day (PND) 7 cerebellum in C57BL/6J mice using a previously described protocol (Iwata-Ichikawa et al, 1999). All protocols followed in this study are described in our previous work (Jin et al, 2020).…”