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微小RNA-107通过靶向Dicer-1促进中风后血管生成。

MicroRNA-107 contributes to post-stroke angiogenesis by targeting Dicer-1.

作者信息

Li Yanan, Mao Ling, Gao Yuan, Baral Suraj, Zhou Yifan, Hu Bo

机构信息

Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

出版信息

Sci Rep. 2015 Aug 21;5:13316. doi: 10.1038/srep13316.

DOI:10.1038/srep13316
PMID:26294080
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4543985/
Abstract

Previous studies have suggested that microRNA-107 (miR-107) regulates cell migration in tumor and promotes Hypoxia Inducible Factor 1α (HIF1α) regulated angiogenesis under hypoxia. We found that miR-107 was strongly expressed in ischemic boundary zone (IBZ) after permanent middle cerebral artery occlusion (pMCAO) in rats and inhibition of miR-107 could reduce capillary density in the IBZ after stroke. Such finding led us to hypothesize that miR-107 might regulate post-stroke angiogenesis and therefore serve as a therapeutic target. We also found that antagomir-107, a synthetic miR-107 inhibitor, decreased the number of capillaries in IBZ and increased overall infarct volume after pMCAO in rats. We demonstrated that miR-107 could directly down-regulate Dicer-1, a gene that encodes an enzyme essential for processing microRNA (miRNA) precursors. This resulted in translational desupression of VEGF (vascular endothelial growth factor) mRNA, thereby increasing expression of endothelial cell-derived VEGF (VEGF165/VEGF164), leading to angiogenesis after stroke. This process might be a protective mechanism for ischemia-induced cerebral injury and miR-107 might be used as a novel tool in stroke treatment.

摘要

先前的研究表明，微小RNA-107（miR-107）在肿瘤中调节细胞迁移，并在缺氧条件下促进缺氧诱导因子1α（HIF1α）调节的血管生成。我们发现，在大鼠永久性大脑中动脉闭塞（pMCAO）后，miR-107在缺血边界区（IBZ）中强烈表达，抑制miR-107可降低中风后IBZ中的毛细血管密度。这一发现使我们推测，miR-107可能调节中风后的血管生成，因此可作为治疗靶点。我们还发现，抗miR-107（一种合成的miR-107抑制剂）可减少大鼠pMCAO后IBZ中的毛细血管数量，并增加总体梗死体积。我们证明，miR-107可直接下调Dicer-1，该基因编码一种处理微小RNA（miRNA）前体所必需的酶。这导致血管内皮生长因子（VEGF）mRNA的翻译抑制，从而增加内皮细胞衍生的VEGF（VEGF165/VEGF164）的表达，导致中风后血管生成。这一过程可能是缺血性脑损伤的一种保护机制，miR-107可能用作中风治疗的新工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a3/4543985/0114693ed767/srep13316-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a3/4543985/3ed0e18a384a/srep13316-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a3/4543985/ab0bb9e4507a/srep13316-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a3/4543985/b62079afc8e5/srep13316-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a3/4543985/3f37aff01232/srep13316-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a3/4543985/74133661b446/srep13316-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a3/4543985/0114693ed767/srep13316-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a3/4543985/3ed0e18a384a/srep13316-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a3/4543985/ab0bb9e4507a/srep13316-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a3/4543985/b62079afc8e5/srep13316-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a3/4543985/3f37aff01232/srep13316-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a3/4543985/74133661b446/srep13316-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a3/4543985/0114693ed767/srep13316-f6.jpg

相似文献

[1]
MicroRNA-107 contributes to post-stroke angiogenesis by targeting Dicer-1.

Sci Rep. 2015-8-21

[2]
MicroRNA-493 regulates angiogenesis in a rat model of ischemic stroke by targeting MIF.

FEBS J. 2016-5

[3]
lncRNAs HIF1A-AS2 facilitates the up-regulation of HIF-1α by sponging to miR-153-3p, whereby promoting angiogenesis in HUVECs in hypoxia.

Biomed Pharmacother. 2017-10-4

[4]
MicroRNA-384-5p Promotes Endothelial Progenitor Cell Proliferation and Angiogenesis in Cerebral Ischemic Stroke through the Delta-Likeligand 4-Mediated Notch Signaling Pathway.

Cerebrovasc Dis. 2020

[5]
MiR-150 Regulates Poststroke Cerebral Angiogenesis via Vascular Endothelial Growth Factor in Rats.

CNS Neurosci Ther. 2016-2-28

[6]
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Mol Med Rep. 2016-5

[7]
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Aging (Albany NY). 2019-5-7

[8]
WSS25 inhibits Dicer, downregulating microRNA-210, which targets Ephrin-A3, to suppress human microvascular endothelial cell (HMEC-1) tube formation.

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[9]
MicroRNA-210 Promotes Accumulation of Neural Precursor Cells Around Ischemic Foci After Cerebral Ischemia by Regulating the SOCS1-STAT3-VEGF-C Pathway.

J Am Heart Assoc. 2018-2-25

[10]
miR-210 activates notch signaling pathway in angiogenesis induced by cerebral ischemia.

Mol Cell Biochem. 2012-7-26

引用本文的文献

[1]
Advancing Ischemic Stroke Prognosis: Key Role of MiR-155 Non-Coding RNA.

Int J Mol Sci. 2025-4-22

[2]
Aminophylline targets miR-128-3p/Slc7a11 axis to attenuate neuronal ferroptosis after traumatic brain injury.

Cell Mol Life Sci. 2025-2-22

[3]
Mechanisms of Postischemic Stroke Angiogenesis: A Multifaceted Approach.

J Inflamm Res. 2024-7-12

[4]
Molecular Pathogenesis of Ischemic and Hemorrhagic Strokes: Background and Therapeutic Approaches.

Int J Mol Sci. 2024-6-7

[5]
Small RNA signatures of acute ischemic stroke in L1CAM positive extracellular vesicles.

Sci Rep. 2024-6-12

[6]
MiRNAs as potential therapeutic targets and biomarkers for non-traumatic intracerebral hemorrhage.

Biomark Res. 2024-2-2

[7]
MicroRNA Profiles in Critically Ill Patients.

Curr Med Chem. 2024

[8]
Angiogenesis after ischemic stroke.

Acta Pharmacol Sin. 2023-7

[9]
MicroRNAs in spinal cord injury: A narrative review.

Front Mol Neurosci. 2023-2-2

[10]
Gastrodin ameliorates the lipopolysaccharide-induced neuroinflammation in mice by downregulating miR-107-3p.

Front Pharmacol. 2022-12-8

本文引用的文献

[1]
VEGF-A165 potently induces human blood-nerve barrier endothelial cell proliferation, angiogenesis, and wound healing in vitro.

Cell Mol Neurobiol. 2013-5-26

[2]
miR-210 suppresses BNIP3 to protect against the apoptosis of neural progenitor cells.

Stem Cell Res. 2013-7

[3]
Hypoxia-responsive miRNAs target argonaute 1 to promote angiogenesis.

J Clin Invest. 2013-2-15

[4]
MiR-155 at the heart of oncogenic pathways.

Oncogene. 2013-2-18

[5]
Sonic hedgehog (Shh) regulates the expression of angiogenic growth factors in oxygen-glucose-deprived astrocytes by mediating the nuclear receptor NR2F2.

Mol Neurobiol. 2013-2-3

[6]
Functional importance of Dicer protein in the adaptive cellular response to hypoxia.

J Biol Chem. 2012-6-28

[7]
Vascular endothelial cell-specific microRNA-15a inhibits angiogenesis in hindlimb ischemia.

J Biol Chem. 2012-6-12

[8]
Inhibitory effects of microRNA-34a on cell migration and invasion of invasive urothelial bladder carcinoma by targeting Notch1.

J Huazhong Univ Sci Technolog Med Sci. 2012-6

[9]
Astrocyte-derived VEGF-A drives blood-brain barrier disruption in CNS inflammatory disease.

J Clin Invest. 2012-6-1

[10]
Angiogenesis: a harmonized target for recovery after stroke.

Stroke. 2012-8

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