LncRNA MALAT1 aggravates oxygen‐glucose deprivation/reoxygenation-induced neuronal endoplasmic reticulum stress and apoptosis via the miR-195a-5p/HMGA1 axis

Abstract

Background This study aimed to investigate the potential role and molecular mechanism of lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in cerebral ischemia/reperfusion injury. Results Using an oxygen-glucose deprivation/reoxygenation (OGD/R) cell model, we determined that the expression of MALAT1 was significantly increased during OGD/R. MALAT1 knockdown reversed OGD/R-induced apoptosis and ER stress. Mechanistically, MALAT1 promoted OGD/R-induced neuronal injury through sponging miR-195a-5p to upregulating high mobility group AT-hook1 (HMGA1). Conclusions Collectively, these data demonstrate the mechanism underlying the invovlvement of MALAT1 in cerebral ischemia/reperfusion injury, thus providing translational evidence that MALAT1 may serve as a novel biomarker and therapeutic target for ischemic stroke.

Long Non-Coding RNA-Mediated Competing Endogenous RNA Networks in Ischemic Stroke: Molecular Mechanisms, Therapeutic Implications, and Challenges

“…LncRNA MALAT1 has been reported to be highly expressed in both in vivo and in vitro models of ischemia ( Guo et al, 2017 ; Zhang G. et al, 2020 ; Jia et al, 2021 ). In addition, It has also been claimed that downregulation of MALAT1 expression alleviates neuronal apoptosis.…”

“…Furthermore, miR-375 targets both MALAT1 and phosphodiesterase 4D (PDE4D) ( Zhang G. et al, 2020 ). It has also been reported that MALAT1 knockdown causes a reversal in OGD/R-induced apoptosis and endoplasmic reticulum stress through the targeting of miR-195a-5p and regulating the expression of high mobility group AT-hook1 (HMGA1) ( Jia et al, 2021 ).…”

“…The functions of LncRNA MALAT1 have been examined in different brain cells in previous studies. MALAT1 expression is upregulated after OGD/R treatment in neurons, BV-2 cells, and astrocytes, which results in MALAT1 acting as a harmful factor in I/R injury by promoting cell death via apoptosis and inflammation ( Guo et al, 2017 ; Wang H. et al, 2020 ; Zhang G. et al, 2020 ; Cao et al, 2020 ; Jia et al, 2021 ). However, MALAT1 plays a protective role in BMECs subjected to OGD/R because it reduces apoptosis and promotes angiogenesis ( Li Z. et al, 2017 ; Gao C. et al, 2020 ; Gao and Wang 2020 ).…”

Alteration in Long Noncoding RNAs in Response to Oxidative Stress and Ladostigil in SH-SY5Y Cells

“…As a general theme, many lncRNAs act via sponging of specific miRNAs (e.g., [68,69]). For example, MALAT1 promotes oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neuronal injury through ceRNA mechanisms [32,33]. Similarly, the beneficial effect of NORAD on cell survival was attributed to its miRNA sponging capacity [70].…”

“…Among these uncharacterized ncRNAs is MALAT1 (Metastasis-associated lung adenocarcinoma transcript 1; expression level ranked 99.94% of all ncRNA-expressed genes). The MALAT1 gene was shown to have a neuroprotective role in AD and Parkinson's disease (PD) [32,33]. MALAT1 also protects hippocampal neurons against autophagy, apoptosis [34] and ischemia [35].…”