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Role of METTL3-Dependent N6-Methyladenosine mRNA Modification in the Promotion of Angiogenesis.
Yao, Mu-Di; Jiang, Qin; Ma, Yan; Liu, Chang; Zhu, Chuan-Yan; Sun, Ya-Nan; Shan, Kun; Ge, Hui-Min; Zhang, Qiu-Yang; Zhang, Hui-Ying; Yao, Jin; Li, Xiu-Miao; Yan, Biao.
Afiliação
  • Yao MD; Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China; The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China; The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
  • Jiang Q; The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China; The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
  • Ma Y; The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China; The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
  • Liu C; Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China; The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China; The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
  • Zhu CY; The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China; The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
  • Sun YN; Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China.
  • Shan K; Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China.
  • Ge HM; The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China; The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
  • Zhang QY; The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China; The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
  • Zhang HY; The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China; The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
  • Yao J; The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China; The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
  • Li XM; The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China; The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
  • Yan B; Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai 200031, China; Shanghai Key Laboratory of Visual Impairment and Re
Mol Ther ; 28(10): 2191-2202, 2020 10 07.
Article em En | MEDLINE | ID: mdl-32755566
ABSTRACT
Epigenetic alterations occur in many physiological and pathological processes. N6-methyladenosine (m6A) modification is the most prevalent modification in eukaryotic mRNAs. However, the role of m6A modification in pathological angiogenesis remains elusive. In this study, we showed that the level of m6A modification was significantly upregulated in endothelial cells and mouse retinas following hypoxic stress, which was caused by increased METTL3 levels. METTL3 silencing or METTL3 overexpression altered endothelial cell viability, proliferation, migration, and tube formation in vitro. METTL3 knockout in vivo decreased avascular area and pathological neovascular tufts in an oxygen-induced retinopathy model and inhibited alkali burn-induced corneal neovascularization. Mechanistically, METTL3 exerted its angiogenic role by regulating Wnt signaling through the m6A modification of target genes (e.g., LRP6 and dishevelled 1 [DVL1]). METTL3 enhanced the translation of LRP6 and DVL1 in an YTH m6A RNA-binding protein 1 (YTHDF1)-dependent manner. Collectively, this study suggests that METTL3-mediated m6A modification is an important hypoxic stress-response mechanism. The targeting of m6A through its writer enzyme METTL3 is a promising strategy for the treatment of angiogenic diseases.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: RNA Mensageiro / Adenosina / Regulação da Expressão Gênica / Epigênese Genética / Metiltransferases / Neovascularização Patológica Tipo de estudo: Etiology_studies Limite: Animals / Humans Idioma: En Revista: Mol Ther Assunto da revista: BIOLOGIA MOLECULAR / TERAPEUTICA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: China
Texto completo
Imprimir
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PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: RNA Mensageiro / Adenosina / Regulação da Expressão Gênica / Epigênese Genética / Metiltransferases / Neovascularização Patológica Tipo de estudo: Etiology_studies Limite: Animals / Humans Idioma: En Revista: Mol Ther Assunto da revista: BIOLOGIA MOLECULAR / TERAPEUTICA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: China