FTO regulates ocular angiogenesis via m6A-YTHDF2-dependent mechanism.
Exp Eye Res
; 197: 108107, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-32531187
ABSTRACT
Pathological ocular angiogenesis commonly results in visual impairment or even blindness. Unveiling the mechanisms of pathological angiogenesis is critical to identify the regulators and develop effective targeted therapies. Here, we used corneal neovascularization (CNV) model to investigate the mechanism of pathological ocular angiogenesis. We show that N6-methyladenosine (m6A) mRNA demethylation mediated by fat mass- and obesity-associated protein (FTO) could regulate endothelial cell (EC) function and pathological angiogenesis during CNV. FTO levels are increased in neovascularized corneas and ECs under pathological conditions. In vitro silencing of FTO in ECs results in reduced cellular proliferation, migration, and tube formation under both basal and pathological conditions. Furthermore, FTO silencing attenuates suture-induced CNV in vivo. Mechanically, FTO silencing in ECs could increase m6A methylation levels in critical pro-angiogenic genes, such as FAK, leading to decreased RNA stability and increased RNA decay through m6A reader YTHDF2. Our study demonstrates that FTO regulates pathological ocular angiogenesis by controlling EC function in an m6A-YTHDF2-dependent manner.
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Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
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Glicoproteínas de Membrana
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Regulação da Expressão Gênica
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Proteínas de Ligação a RNA
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Neovascularização da Córnea
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Dioxigenase FTO Dependente de alfa-Cetoglutarato
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Proteínas do Tecido Nervoso
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article