Dataset Information

MiR-24 Targets the Transmembrane Glycoprotein Neuropilin-1 in Human Brain Microvascular Endothelial Cells.

ABSTRACT: Neuropilin-1 is a transmembrane glycoprotein that has been implicated in several processes including angiogenesis and immunity. Recent evidence has also shown that it is implied in the cellular internalization of the severe acute respiratory syndrome coronavirus (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19). We hypothesized that specific microRNAs can target Neuropilin-1. By combining bioinformatic and functional approaches, we identified miR-24 as a regulator of Neuropilin-1 transcription. Since Neuropilin-1 has been shown to play a key role in the endothelium-mediated regulation of the blood-brain barrier, we validated miR-24 as a functional modulator of Neuropilin-1 in human brain microvascular endothelial cells (hBMECs), which are the most suitable cell line for an in vitro blood-brain barrier model.

SUBMITTER: Mone P

PROVIDER: S-EPMC7931075 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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miR-24 Targets the Transmembrane Glycoprotein Neuropilin-1 in Human Brain Microvascular Endothelial Cells.

Mone Pasquale P Gambardella Jessica J Wang Xujun X Jankauskas Stanislovas S SS Matarese Alessandro A Santulli Gaetano G

Non-coding RNA 20210202 1

Neuropilin-1 is a transmembrane glycoprotein that has been implicated in several processes including angiogenesis and immunity. Recent evidence has also shown that it is implied in the cellular internalization of the severe acute respiratory syndrome coronavirus (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19). We hypothesized that specific microRNAs can target Neuropilin-1. By combining bioinformatic and functional approaches, we identified miR-24 as a regulator of Neuropilin- ...[more]

PMID: 33540664

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Project description:Background:Hypoxia following ischemic stroke is a common cause of brain insults. Mounting evidence suggests that long non-coding RNAs (lncRNAs) play a vital role in regulating certain physiological and pathological processes including ischemic stroke. For the first time, the present study investigated the effects and mechanism of LncRNA MACC1-AS1 on hypoxia-induced human brain microvascular endothelial cells (HBMECs). Methods:LncRNA MACC1-AS1 levels in HBMECs were detected via reverse transcription quantitative polymerase chain reaction (RT-qPCR) assay. Reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT), were detected using their respective kits. Flow cytometry and clone formation assay were performed to evaluate the effects of lncRNA MACC1-AS1 on cell apoptosis and cell proliferation respectively. Angiogenesis capacity was evaluated via tube formation assay. Transwell migration assay was performed for assessment of cell migration, Western blot assay was performed for measurement of Twist1 and VE-cadherin level, and permeability assay was performed for evaluation of the cell barrier function. The target gene was predicted via bioinformatics online tool and validated through luciferase reporter assay and RNA pull-down assay. Results:LncRNA MACC1-AS1 was downregulated in hypoxia-induced HBMECs. Overexpression of LncRNA MACC1-AS1 reduced cell apoptosis and oxidative stress, while promoting cell proliferation, migration, and angiogenesis. Moreover, LncRNA MACC1-AS1 overexpression reduced cell permeability and elevated VE-cadherin level, which contributed to maintaining cell barrier function. TWIST1 was validated as the target of miR-6867-5p which was further targeted by lncRNA MACC1-AS1. Thus, LncRNA MACC1-AS1 functions in hypoxia-induced HBMECs by regulating miR-6867-5p/TWIST1. Conclusions:In this study, we found that LncRNA MACC1-AS1 exerted a protective role in hypoxia-induced HBMECs via regulating miR-6867-5p/TWIST1, indicating a new therapeutic strategy for future ischemic stroke therapy.

Dataset Information

MiR-24 Targets the Transmembrane Glycoprotein Neuropilin-1 in Human Brain Microvascular Endothelial Cells.

Publications

miR-24 Targets the Transmembrane Glycoprotein Neuropilin-1 in Human Brain Microvascular Endothelial Cells.

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