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PXD029706

PXD029706 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAn integrative multi-omics analysis reveals microRNA-143 as potential therapeutics to attenuate retinal angiogenesis
DescriptionRetinal neovascularization is a severe complication of several neovascular retinal diseases, including proliferative diabetic retinopathy, central retinal vein occlusion and retinopathy of prematurity. MicroRNAs (miRNAs) are master regulators of gene expression that play an important role in retinal neovascularization. Here, we investigate the retinal miRNA expression profile in a rat model of oxygen-induced retinopathy (OIR) using miRNA-Seq. We show that miR-143-3p, miR-126-3p, and miR-150-5p are significantly downregulated in the retina of OIR rats, and intravitreal injection of synthetic mimics of these miRNAs significantly ameliorate retinal neovascularization in this animal model. Of these identified miRNAs, miR-143 which is highly expressed in the neural retina and retinal vasculature is here identified for the first time to be associated with retinal neovascularization. With a focus on miR-143 expression in primary human retinal endothelial cells, we explore its involved pathways through a multi-omics analysis. In miR-143 treated cells, the functional evaluation showed a decrease in cell migration and delayed endothelial vessel-like tube remodelling. Consequently, the multi-omics analysis suggests that miR-143 negatively impacts endothelial cell activity through regulating cell-matrix adhesion and mediating HIF signalling pathway. Furthermore, using cytoHubba, a topological analysis method to assess the essentiality of genes, we predict 20 top hub genes regulated by miR-143 that may be involved in mediating endothelial cell function. Using CIBERSORTx, a bulk gene expression deconvolution algorithm, we analyze a public RNA-Seq dataset (GSE102485) and demonstrate that the retinal neovascular membranes in patients with proliferative diabetic retinopathy (PDR) principally consist of endothelial cells. We then identify 2 hub genes, THBS1 and SERPINE1, direct targets of miR-143, which on further analysis demonstrate an expression level significantly altered in the PDR patients compared to controls. These findings suggest that miR-143 appears to be essential for limiting endothelial cell-matrix adhesion, thus suppressing retinal neovascularization. The present study might have important implications for the exploration of potential therapeutic targets for the treatment of neovascular ocular diseases.
HostingRepositoryPRIDE
AnnounceDate2026-06-29
AnnouncementXMLSubmission_2026-06-28_19:17:32.288.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterRichard Wilson
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-11-12 06:06:41ID requested
12026-06-28 19:17:33announced
Publication List
10.1089/nat.2021.0111;
Wang JH, Chuang YF, Chen J, Singh V, Lin FL, Wilson R, Tu L, Ma C, Wong RCB, Wang PY, Zhong J, Hewitt AW, van Wijngaarden P, Dusting GJ, Liu GS, An Integrative Multi-Omics Analysis Reveals MicroRNA-143 as a Potential Therapeutic to Attenuate Retinal Angiogenesis. Nucleic Acid Ther, 32(4):251-266(2022) [pubmed]
Keyword List
submitter keyword: MicroRNA, Endothelial cells, Oxygen-induced retinopathy,Retinal neovascularization, Next-generation sequencing
Contact List
Dr Richard Wilson
contact affiliationProteomics facility, Central Science Laboratory, University of Tasmania
contact emailrichard.wilson@utas.edu.au
lab head
Richard Wilson
contact affiliationUniversity of Tasmania
contact emailrichard.wilson@utas.edu.au
dataset submitter
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