A novel regulatory network of linc00174/miR-150-5p/VEGFA modulates pathological angiogenesis in diabetic retinopathy.
Can J Physiol Pharmacol
; 99(11): 1175-1183, 2021 Nov.
Article
em En
| MEDLINE
| ID: mdl-34081870
ABSTRACT
Diabetic retinopathy (DR) has been regarded as a sight-threatening vascular complication of diabetes mellitus. Accumulating evidence has identified the involvement of long non-coding RNAs (lncRNAs) in DR pathogenesis. We aim to investigate the role and underlying mechanism of linc00174 in the DR process. Samples of human vitreous humour from proliferative DR and non-diabetic individuals were collected to examine the levels of linc00174. Human retinal microvascular endothelial cells (HRMECs) exposed with high glucose (HG) were employed to simulate the pathological statues of DR. Short hairpin RNA specifically targeting linc00174 was applied. CCK-8, transwell, and matrigel tube formation were performed to evaluate cell proliferation, migration, and angiogenesis. Bioinformatics analysis and luciferase reporter assay were conducted to verify the linc00174/miR-150-5p/vascular endothelial growth factor A (VEGFA) regulatory network. Western blotting was employed to determine the expression of VEGFA. Linc00174 was significantly elevated in patients with DR, as well as HG-stimulated HRMECs, of which knockdown repressed HG-induced proliferation, migration, and angiogenesis. miR-150-5p was identified as a downstream effector to be involved in linc00174-mediated protective effects. miR-150-5p directly bound to the 3' untranslated region of VEGFA. The linc00174/miR-150-5p/VEGFA axis was confirmed in retinal vascular dysfunction. The linc00174 deteriorates diabetic retinal microangiopathy via regulating miR-150-5p/VEGFA pathway, indicating a novel therapeutic target for DR treatment.
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Base de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica no Desenvolvimento
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MicroRNAs
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Fator A de Crescimento do Endotélio Vascular
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Retinopatia Diabética
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RNA Longo não Codificante
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Neovascularização Patológica
Tipo de estudo:
Prognostic_studies
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Can J Physiol Pharmacol
Ano de publicação:
2021
Tipo de documento:
Article