Long noncoding RNA MALAT1 inhibits apoptosis induced by oxygen-glucose deprivation and reoxygenation in human brain microvascular endothelial cells

Xin,Jia‑Wei; Jiang,Yu‑Gang

doi:10.3892/etm.2017.4095

Long noncoding RNA MALAT1 inhibits apoptosis induced by oxygen-glucose deprivation and reoxygenation in human brain microvascular endothelial cells

Authors:
- Jia‑Wei Xin
- Yu‑Gang Jiang
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Affiliations: Department of Neurosurgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China
Published online on: February 2, 2017 https://doi.org/10.3892/etm.2017.4095
Pages: 1225-1234
Copyright: © Xin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cerebral ischemia/reperfusion (I/R) injury leads to brain vascular dysfunction, which is characterized by endothelial cell injury or death. Long noncoding (lnc) RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is reportedly associated with endothelial cell functions and dysfunctions. In the present study, the role of MALAT1 in I/R-induced cerebral vascular endothelial cell apoptosis was explored using oxygen‑glucose deprivation and reoxygenation (OGD‑R) as an in vitro I/R injury model. Primary human brain microvascular endothelial cells were cultured under OGD‑R, and the expression levels of MALAT1 and cell apoptosis were measured at 6, 9, 12, 24 and 36 h post‑reoxygenation. The expression levels of MALAT1 and the apoptotic rate of cells exposed to OGD-R exhibited contrasting trends following reoxygenation. Following OGD‑R, lentiviral overexpression of MALAT1 increased phosphatidylinositol 3‑kinase (PI3K) activities and the activation of Akt phosphorylation, and decreased cell apoptosis and caspase 3 activities, which were successfully abolished by treatment with a PI3K inhibitor, Wortmannin. Conversely, lentiviral knockdown of MALAT1 decreased PI3K activities and the activation of Akt phosphorylation, and increased cell apoptosis and caspase 3 activity. Overexpression and knockdown of MALAT1 exhibited no significant effects on OGD‑R‑induced reactive oxygen species (ROS) production. In conclusion, to the best of our knowledge, the present study was the first to suggest that lncRNA MALAT1 may protect human brain vascular endothelial cells from OGD‑R‑induced apoptosis via a PI3K‑dependent mechanism. These findings suggest that MALAT1 may be a potential novel therapeutic target for cerebral I/R injury.

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