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LncRNA MALAT1 Promotes OGD-Induced Apoptosis of Brain Microvascular Endothelial Cells by Sponging miR-126 to Repress PI3K/Akt Signaling Pathway

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Abstract

Ischemic stroke (IS) is a common disease that seriously endangers human health. Patients with IS present with increased death of brain microvascular endothelial cells (BMECs). MALAT1 is found to be upregulated in IS patients. However, the function of MALAT1 in IS pathogenesis still remains unclear. This study aimed to investigate the role of MALAT1 in IS in vitro model and the related molecular mechanisms. The expressions of MALAT1 and miR-126 were detected by qPCR. The in vitro IS model was established by treating BMECs with oxygen-glucose deprivation (OGD). Cell viability and cell apoptosis were assessed by MTT assay and flow cytometry, respectively. Luciferase assay was conducted to examine the interplay between MALAT1 and miR-126. Western blotting was used to determine the protein levels of apoptosis-associated proteins (e.g. caspase 3, Bax and Bcl-2) and PI3K/Akt pathway-related proteins (e.g. PI3K, Akt, p-PI3K, p-Akt). OGD induced upregulation of MALAT1 and downregulation of miR-126 in HBMECs. MALAT1 knockdown promoted the proliferation of HBMECs and reduced the proportion of apoptotic HBMECs by regulating the expression of apoptosis-related proteins. MALAT1 targeted and negatively regulated miR-126 expression. Overexpression of miR-126 activated the PI3K/Akt pathway, which in turn affected the proliferation and apoptosis of HBMECs. MALAT1 negatively regulated PI3K/Akt pathway. MALAT1 inhibited the proliferation and induced the apoptosis of OGD-induced HBMECs through suppressing PI3K/AKT pathway by sponging miR-126, providing a potential therapeutic target for IS.

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Abbreviations

IS:

Ischemic stroke

BMECs:

Brain microvascular endothelial cells

ncRNA:

Non-coding RNA

lncRNA:

Long non-coding RNA

miRNA:

microRNA

MALAT1:

Metastasis-associate lung adenocarcinoma transcript 1

HBMECs:

Human brain microvascular endothelial cells

ATCC:

American type culture collection

FBS:

Fetal bovine serum

CST:

Cell signaling technology

OGD:

Oxygen-glucose deprivation

PI:

Propidium iodide

qRT-PCR:

Quantitative reverse transcription polymerase chain reaction

RIPA buffer:

Radioimmunoprecipitation assay buffer

BCA:

Bicinchoninic acid

BSA:

Bovine serum albumin

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Acknowledgements

This work was supported by Guizhou Province Traditional Chinese Medicine Administration, National Medical Science and Technology Research Project [Grant Number QZYY-2019-021], The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine Research projects in the hospital (Grant Number GZEYK[2020]11) and Guizhou University of Traditional Chinese Medicine 2019 Campus Project.

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Authors and Affiliations

  1. Department of Neurology, The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, 550003, Guiyang, People’s Republic of China

    Lin Zhang & Hui Yang

  2. Hunan University of Traditional Chinese Medicine, 410007, Changsha, People’s Republic of China

    Wen-Juan Li

  3. Department of Neurology, The Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine, No.233 CaiE North Road, Kaifu District, Changsha, 410005, Hunan Province, People’s Republic of China

    Ye-Hui Liu

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  1. Lin Zhang
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  2. Hui Yang
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Correspondence to Ye-Hui Liu.

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Zhang, L., Yang, H., Li, WJ. et al. LncRNA MALAT1 Promotes OGD-Induced Apoptosis of Brain Microvascular Endothelial Cells by Sponging miR-126 to Repress PI3K/Akt Signaling Pathway. Neurochem Res 45, 2091–2099 (2020). https://doi.org/10.1007/s11064-020-03071-6

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  • DOI: https://doi.org/10.1007/s11064-020-03071-6

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