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An integrative multi-omics analysis reveals microRNA-143 as a potential therapeutic to attenuate retinal angiogenesis

Citation

Wang, JH and Chuang, Y-F and Chen, J and Singh, V and Lin, F-L and Wilson, R and Tu, L and Ma, C and Wong, RCB and Wang, PY and Zhong, J and Hewitt, AW and Van Wijngaarden, P and Dusting, GJ and Liu, G-S, An integrative multi-omics analysis reveals microRNA-143 as a potential therapeutic to attenuate retinal angiogenesis, Nucleic Acid Therapeutics, 32, (4) pp. 251-266. ISSN 2159-3337 (2022) [Refereed Article]

DOI: doi:10.1089/nat.2021.0111

Abstract

Retinal neovascularization is a severe complication of proliferative diabetic retinopathy (PDR). MicroRNAs (miRNAs) are master regulators of gene expression that play an important role in retinal neovascularization. In this study, we show that miR-143-3p is significantly downregulated in the retina of a rat model of oxygen-induced retinopathy (OIR) by miRNA-sequencing. Intravitreal injection of synthetic miR-143 mimics significantly ameliorate retinal neovascularization in OIR rats. miR-143 is identified to be highly expressed in the neural retina particularly in the ganglion cell layer and retinal vasculature. In miR-143 treated cells, the functional evaluation showed a decrease in cell migration and delayed endothelial vessel-like tube remodeling. The multiomics analysis suggests that miR-143 negatively impacts endothelial cell activity through regulating cell-matrix adhesion and mediating hypoxia-inducible factor-1 signaling. We predict hub genes regulated by miR-143 that may be involved in mediating endothelial cell function by cytoHubba. We also demonstrate that the retinal neovascular membranes in patients with PDR principally consist of endothelial cells by CIBERSORTx. We then identify 2 hub genes, thrombospondin 1 and plasminogen activator inhibitor, direct targets of miR-143, that significantly altered in the PDR patients. These findings suggest that miR-143 appears to be essential for limiting endothelial cell-matrix adhesion, thus suppressing retinal neovascularization.

Item Details

Item Type:Refereed Article
Keywords:endothelial cell, microRNA, oxygen-induced retinopathy, proteomics, retinal neovascularization, transcriptomics
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Treatment of human diseases and conditions
UTAS Author:Chuang, Y-F (Dr Yu-Fan Chuang)
UTAS Author:Singh, V (Dr Vikrant Singh)
UTAS Author:Lin, F-L (Dr Fan-Li Lin)
UTAS Author:Wilson, R (Dr Richard Wilson)
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
ID Code:154959
Year Published:2022
Deposited By:Menzies Institute for Medical Research
Deposited On:2023-01-20
Last Modified:2023-01-20
Downloads:0

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