Dataset Information

The long noncoding RNA Malat1: Its physiological and pathophysiological functions.

ABSTRACT: Recent studies suggest that in humans, DNA sequences responsible for protein coding regions comprise only 2% of the total genome. The rest of the transcripts result in RNA transcripts without protein-coding ability, including long noncoding RNAs (lncRNAs). Different from most members in the lncRNA family, the metastasis-associated lung adenocarcinoma transcript 1 (Malat1) is abundantly expressed and evolutionarily conserved throughout various mammalian species. Malat1 is one of the first identified lncRNAs associated with human disease, and cumulative studies have indicated that Malat1 plays critical roles in the development and progression of various cancers. Malat1 is also actively involved in various physiologic processes, including alternative splicing, epigenetic modification of gene expression, synapse formation, and myogenesis. Furthermore, extensive evidences show that Malat1 plays pivotal roles in multiple pathological conditions as well. In this review, we will summarize latest findings related to the physiologic and pathophysiological processes of Malat1 and discuss its therapeutic potentials.

SUBMITTER: Zhang X

PROVIDER: S-EPMC5731810 | biostudies-other | 2017 Dec

REPOSITORIES: biostudies-other

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The long noncoding RNA Malat1: Its physiological and pathophysiological functions.

Zhang Xuejing X Hamblin Milton H MH Yin Ke-Jie KJ

RNA biology 20171006 12

Recent studies suggest that in humans, DNA sequences responsible for protein coding regions comprise only 2% of the total genome. The rest of the transcripts result in RNA transcripts without protein-coding ability, including long noncoding RNAs (lncRNAs). Different from most members in the lncRNA family, the metastasis-associated lung adenocarcinoma transcript 1 (Malat1) is abundantly expressed and evolutionarily conserved throughout various mammalian species. Malat1 is one of the first identif ...[more]

PMID: 28837398

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Project description:The study was designed to determine the role of long noncoding RNA (lncRNA), metastasis-associated lung adenocarcinoma transcript 1 (Malat1), in ischemic stroke outcome. Primary mouse brain microvascular endothelial cells (BMECs) were cultured and treated with Malat1 GapmeR before 16 h oxygen and glucose depravation (OGD). Cell death was assayed by LDH and MTT methods. Malat1 knock-out and wild-type mice were subjected to 1 h of middle cerebral artery occlusion (MCAO) and 24-72 h of reperfusion. To explore the underlying mechanism, apoptotic and inflammatory factors were measured by qPCR, ELISA, and Western blotting. The physical interaction between Malat1 and apoptotic or inflammatory factors was measured by RNA immunoprecipitation. Increased Malat1 levels were found in cultured mouse BMECs after OGD as well as in isolated cerebral microvessels in mice after MCAO. Silencing of Malat1 by Malat1 GapmeR significantly increased OGD-induced cell death and Caspase 3 activity in BMECs. Silencing of Malat1 also significantly aggravated OGD-induced expression of the proapoptotic factor Bim and proinflammatory cytokines MCP-1, IL-6, and E-selectin. Moreover, Malat1 KO mice presented larger brain infarct size, worsened neurological scores, and reduced sensorimotor functions. Consistent with in vitro findings, significantly increased expression of proapoptotic and proinflammatory factors was also found in the cerebral cortex of Malat1 KO mice after ischemic stroke compared with WT controls. Finally, we demonstrated that Malat1 binds to Bim and E-selectin both in vitro and in vivo Our study suggests that Malat1 plays critical protective roles in ischemic stroke.SIGNIFICANCE STATEMENT Accumulative studies have demonstrated the important regulatory roles of microRNAs in vascular and neural damage after ischemic stroke. However, the functional significance and mechanisms of other classes of noncoding RNAs in cerebrovascular pathophysiology after stroke are less studied. Here we demonstrate a novel role of Malat1, a long noncoding RNA that has been originally identified as a prognostic marker for non-small cell lung cancer, in cerebrovascular pathogenesis of ischemic stroke. Our experiments have provided the first evidence that Malat1 plays anti-apoptotic and anti-inflammatory roles in brain microvasculature to reduce ischemic cerebral vascular and parenchymal damages. Our studies also suggest that lncRNAs can be therapeutically targeted to minimize poststroke brain damage.

Dataset Information

The long noncoding RNA Malat1: Its physiological and pathophysiological functions.

Publications

The long noncoding RNA Malat1: Its physiological and pathophysiological functions.

Similar Datasets

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