Long non‐coding RNA MALAT1 regulates angiogenesis following oxygen‐glucose deprivation/reoxygenation

Abstract

Long non‐coding RNAs (lncRNAs) have been identified as playing critical roles in multiple diseases. However, little is known regarding their roles and mechanisms in post‐stroke angiogenesis. Our studies focused on deciphering the functional roles and the underlying mechanisms of the lncRNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) in the process of angiogenesis following oxygen‐glucose deprivation/reoxygenation (OGD/R). We characterized the up‐regulation of MALAT1 expression in the process of angiogenesis after hypoxic injury in vivo and in vitro. We further showed that compared with the empty vector, MALAT1 knockdown had significantly reduced the capacity for angiogenesis, which was measured by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium (MTT), scratching, cell cycle and immunofluorescent staining. Thus, our findings suggest that MALAT1 may mediate proangiogenic function in OGD/R. To further explore the potential mechanisms, we used lentiviruses expressing shMALAT1 and empty vector; the results revealed that shMALAT1 reduced the expression of 15‐lipoxygenase 1 (15‐LOX1), vascular endothelial growth factor (VEGF) and the phosphorylation of signal transducers and activators of transcription 3 (pSTAT3). Taken together, our results are the first to propose that MALAT1 may regulate angiogenesis through the 15‐LOX1/STAT3 signalling pathway, and they may provide a critical target for the treatment of hypoxic injury and an avenue for therapeutic angiogenesis.

The role of lncRNA MALAT1 in cardiovascular disease

“…57 Hypoxia could promote angiogenesis of ECs through vascular endothelial growth factor (VEGF) signaling and also induce expression of MALAT1. [58][59][60][61] MALAT1 knockdown significantly reduced the VEGF expression and the capacity for angiogenesis via inhibition of 15-lipoxygenase 1 (15-LOX1) and the phosphorylation of signal transducers and activators of transcription 3 (pSTAT3). 17…”

The role of the red blood cell and platelet in the evolution of mammalian and avian endothermy

“…It is proposed, in this review, that the increase in blood vessel density in endotherms compared to ectotherms was initiated during the Permian-Triassic period in response to the low O 2 atmosphere due to hypoxic stimulation of angiogenic factors, based upon studies with mammalian systems (Fraisl, Mazzone, Schmidt, & Carmeliet, 2009;Hashimoto & Shibasaki, 2015;Pugh & Ratcliffe, 2003;Wang, Qu, Suo, & Zhu, 2019). Mammalian vascular cells possess O 2 sensors that interact with the hypoxia-inducible factor (HIF) family (currently there are three known forms).…”

A genetic variant in the promoter of lncRNA MALAT1 is related to susceptibility of ischemic stroke

“…MALAT1, one of the most highly upregulated lncRNAs, was further confirmed to promote angiogenesis and autophagy while reduce apoptosis and inflammation both in vitro and in vivo [15][16][17]. For example, MALAT1 reduced ischemic cerebral damages by regulating 15-LOX1, VEGF and STAT3 related to angiogenesis [15], and acting a competing endogenous RNA for miR-26b to upregulate autophagy factor ULK2 expression directly [16]. Silencing of MALAT1 obviously increased expression of the proapoptotic and proinflammatory cytokines including Bim, IL-6, MCP − 1and Eselectin [17].…”

“…Using RNA sequencing technology, a lot of lncRNAs were abnormally expressed after 16 h under oxygen-glucose deprivation (OGD) condition [14]. MALAT1, one of the most highly upregulated lncRNAs, was further confirmed to promote angiogenesis and autophagy while reduce apoptosis and inflammation both in vitro and in vivo [15][16][17]. For example, MALAT1 reduced ischemic cerebral damages by regulating 15-LOX1, VEGF and STAT3 related to angiogenesis [15], and acting a competing endogenous RNA for miR-26b to upregulate autophagy factor ULK2 expression directly [16].…”