Dataset Information

Long non-coding RNA-MIAT promotes neurovascular remodeling in the eye and brain.

ABSTRACT: Although nervous and vascular systems are functionally different, they usually share similar mechanisms for function maintenance. Neurovascular dysfunction has became the pathogenesis of several vascular and nervous disorders. Here we show that long non-coding RNA-MIAT is aberrantly expressed under neurovascular dysfunction condition. MIAT is shown as a regulator of vascular dysfunction, including retinal angiogenesis, corneal angiogenesis, and vascular permeability. MIAT is also shown as a regulator of retinal neurodegeneration under diabetic condition. Mechanistically, MIAT regulates neural and vascular cell function via MIAT/miR-150-5p/VEGF network. The eye is a valuable model to study central nervous system (CNS) disorders. We show that MIAT knockdown leads to cerebral microvascular degeneration, progressive neuronal loss and neurodegeneration, and behavioral deficits in a CNS neurovascular disorder, Alzheimer's disease. MIAT may represent a pharmacological target for treating neurovascular-related disorders.

SUBMITTER: Jiang Q

PROVIDER: S-EPMC5226539 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Long non-coding RNA-MIAT promotes neurovascular remodeling in the eye and brain.

Jiang Qin Q Shan Kun K Qun-Wang Xiao X Zhou Rong-Mei RM Yang Hong H Liu Chang C Li Yu-Jie YJ Yao Jin J Li Xiu-Miao XM Shen Yi Y Cheng Hong H Yuan Jun J Zhang Yang-Yang YY Yan Biao B

Oncotarget 20160801 31

Although nervous and vascular systems are functionally different, they usually share similar mechanisms for function maintenance. Neurovascular dysfunction has became the pathogenesis of several vascular and nervous disorders. Here we show that long non-coding RNA-MIAT is aberrantly expressed under neurovascular dysfunction condition. MIAT is shown as a regulator of vascular dysfunction, including retinal angiogenesis, corneal angiogenesis, and vascular permeability. MIAT is also shown as a regu ...[more]

PMID: 27391072

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Project description:Blood-tumor barrier (BTB) presents a major obstacle to brain drug delivery. Therefore, it is urgent to enhance BTB permeability for the treatment of glioma. In this study, we demonstrated that MIAT, ZAK, and phosphorylated NFκB-p65 (p-NFκB-p65) were upregulated, while miR-140-3p was downregulated in glioma-exposed endothelial cells (GECs) of BTB compared with those in endothelial cells cocultured with astrocytes (ECs) of blood-brain barrier (BBB). MIAT inhibited miR-140-3p expression, increased the expression of ZAK, enhanced the ratio of p-NFκB-p65:NFκB-p65, and promoted the endothelial leakage of BTB. Our current study revealed that miR-140-3p was complementary to the ZAK 3'untranslated regions (3'-UTR), and luciferase activity of ZAK was inhibited by miR-140-3p in 293T cells. MiR-140-3p silencing resulted in an increase in BTB permeability by targeting ZAK, while overexpression of miR-140-3p had the opposite results in GECs of BTB. Overexpression of ZAK induced an increase in BTB permeability, and this effect was related to ZAK's ability to mediate phosphorylation of NFκB-p65. Conversely, ZAK silencing get opposite results in GECs of BTB. As a molecular sponge of miR-140-3p, MIAT attenuated its negative regulation of the target gene ZAK by adsorbing miR-140-3p. P-NFκB-p65 as a transcription factor negatively regulated the expression of TJ-associated proteins by means of chip assay and luciferase assay. Single or combined application of MIAT and miR-140-3p effectively promoted antitumor drug doxorubicin (Dox) across BTB to induce apoptosis of glioma cells. In summary, MIAT functioned as a miR-140-3p sponge to regulate the expression of its target gene ZAK, which contribution to phosphorylation of NFκB-p65 was associated with an increase in BTB permeability by down-regulating the expression of TJ associated proteins, thereby promoting Dox delivery across BTB. These results might provide a novel strategy and target for chemotherapy of glioma.

Project description:Background: Although the treatment of cancer has made evident progress, its morbidity and mortality are still high. A tumor marker is a critical indicator for early cancer diagnosis, and timely cancer detection can efficiently help improve the prognosis of patients. Therefore, it is necessary to identify novel markers associated with cancer. LncRNA myocardial infarction associated transcript (MIAT) is a newly identified tumor marker, and in this study, we aimed to explore the relationship between MIAT and clinicopathological features and patient prognosis. Methods: We searched PubMed, Embase, Web of Science, and The Cochrane Library from inception to September 2020 to identify correlational studies. Then, we extracted valid data and used Stata software to make forest plots. We used the hazard ratio (HR) or odds ratio (OR) with 95% CI to evaluate the relationship between aberrant expression of MIAT and patients' prognosis and clinicopathological features. Results: The study included 21 studies, containing 2,048 patients. Meta-analysis showed that overexpression of lncRNA MIAT was associated with poor overall survival (OS) (HR = 1.60, 95% CI, 1.31-1.96, p < 0.001). In addition, high expression of MIAT could forecast tumor size (OR = 2.26, 95% CI 1.34-3.81, p = 0.002), distant metastasis (OR = 2.54, 95% CI 1.84-3.50, p < 0.001), TNM stage (OR = 2.38, 95% CI 1.36-4.18, p = 0.002), lymph node metastasis (OR = 2.59, 95% CI 1.25-5.36, p = 0.011), and the degree of differentiation (OR = 2.65, 95% CI 1.54-4.58, p < 0.001). However, other clinicopathological features, including age (OR = 1.07, 95% CI 0.87-1.32, p = 0.516), gender (OR = 0.95, 95% CI 0.77-1.19, p = 0.668), and histology (OR = 0.72, 95% CI 0.48-1.10, p = 0.128) were not significantly different from high expression of MIAT. Conclusions: Our study showed that overexpression of MIAT is related to poor overall survival and clinicopathological features. MIAT can be considered a novel tumor marker to help diagnose tumors earlier and improve patient prognosis.

Dataset Information

Long non-coding RNA-MIAT promotes neurovascular remodeling in the eye and brain.

Publications

Long non-coding RNA-MIAT promotes neurovascular remodeling in the eye and brain.

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