tRNA-derived fragment tRF-1001: A novel anti-angiogenic factor in pathological ocular angiogenesis

Qin Jiang; Yan Ma; Ya Zhao; Mu-Di Yao; Yan Zhu; Qiu-Yang Zhang; Biao Yan

Molecular Therapy: Nucleic Acids (Dec 2022)

tRNA-derived fragment tRF-1001: A novel anti-angiogenic factor in pathological ocular angiogenesis

Qin Jiang,
Yan Ma,
Ya Zhao,
Mu-Di Yao,
Yan Zhu,
Qiu-Yang Zhang,
Biao Yan

Affiliations

Qin Jiang: The Affiliated Eye Hospital, Nanjing Medical University, Nanjing 210000, China; The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing 210000, China
Yan Ma: The Affiliated Eye Hospital, Nanjing Medical University, Nanjing 210000, China; The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing 210000, China
Ya Zhao: The Affiliated Eye Hospital, Nanjing Medical University, Nanjing 210000, China; The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing 210000, China
Mu-Di Yao: Eye Institute, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology, 83# Fen Yang Road, Fudan University, Shanghai 200030, China; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, and Shanghai Key Laboratory of Visual Impairment and Restoration (Fudan University), Shanghai 200030, China
Yan Zhu: The Affiliated Eye Hospital, Nanjing Medical University, Nanjing 210000, China; The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing 210000, China
Qiu-Yang Zhang: The Affiliated Eye Hospital, Nanjing Medical University, Nanjing 210000, China; The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing 210000, China
Biao Yan: Eye Institute, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology, 83# Fen Yang Road, Fudan University, Shanghai 200030, China; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, and Shanghai Key Laboratory of Visual Impairment and Restoration (Fudan University), Shanghai 200030, China; Corresponding author Biao Yan, Fudan University, 83# Fen Yang Road, Shanghai 200030, China.

Journal volume & issue: Vol. 30
pp. 407 – 420

Abstract

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Transfer RNA-derived fragments (tRFs) are a novel class of non-coding RNA transcripts and play important roles in several physiological/pathological processes. However, the role of tRFs in ocular angiogenesis remains elusive. Herein, we investigate whether the intervention of tRF-1001 expression could suppress pathological ocular angiogenesis. The results show that the levels of tRF-1001 expression were reduced in the retinas of an oxygen-induced retinopathy (OIR) model, choroidal neovascularization model, and endothelial sprouting model in vitro. Increased tRF-1001 expression could suppress ocular angiogenesis and endothelial sprouting in vivo and reduce endothelial migration, specification, and sprouting in vitro. Mechanistically, tRF-1001 regulated endothelial angiogenic effects via tRF-1001/METTL3/RBPJ-MAML1 signaling. The levels of tRF-1001 expression were downregulated in the aqueous humor of age-related macular degeneration (AMD) patients. tRF-1001 upregulation could suppress AMD aqueous humor-induced endothelial sprouting and pathological angiogenesis. Collectively, tRF-1001 acts as an anti-angiogenic factor during ocular angiogenesis. Targeting tRF-1001-mediated signaling is a therapeutic option for ocular neovascular diseases.

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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