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Aberrant expression of miR-133a in endothelial cells inhibits angiogenesis by reducing pro-angiogenic but increasing anti-angiogenic gene expression

Ahmed, Suhail; Kurusamy, Sathishkumar; David, Ezra Leander Santhosh; Khan, Kinza; Kalyanakrishnan, Krithika; Ian-Gobo, Miebaka; Kola, Teja Manidhar; Wilkinson, Robert N.; Kannappan, Vinodh; Wang, Weiguang; Gómez, Manuel J.; Redondo, Juan Miguel; Cotton, James; Armesilla, Angel L.

Aberrant expression of miR-133a in endothelial cells inhibits angiogenesis by reducing pro-angiogenic but increasing anti-angiogenic gene expression Thumbnail


Authors

Suhail Ahmed

Sathishkumar Kurusamy

Ezra Leander Santhosh David

Kinza Khan

Krithika Kalyanakrishnan

Miebaka Ian-Gobo

Teja Manidhar Kola

Vinodh Kannappan

Weiguang Wang

Manuel J. Gómez

Juan Miguel Redondo

James Cotton

Angel L. Armesilla



Abstract

Angiogenesis is a multi-factorial physiological process deregulated in human diseases characterised by excessive or insufficient blood vessel formation. Emerging evidence highlights a novel role for microRNAs as regulators of angiogenesis. Previous studies addressing the effect of miR-133a expression in endothelial cells during blood vessel formation have reported conflicting results. Here, we have assessed the specific effect of mature miR-133a strands in angiogenesis and the expression of endothelial angiogenic genes. Transfection of miR-133a-3p or -5p mimics in primary human endothelial cells significantly inhibited proliferation, migration, and tubular morphogenesis of transfected cells. Screening of gene arrays related to angiogenic processes, and further validation by TaqMan qPCR, revealed that aberrant expression of miR-133a-3p led to a decrease in the expression of genes encoding pro-angiogenic molecules, whilst increasing those with anti-angiogenic functions. Ingenuity Pathway Analysis of a collection of genes differentially expressed in cells harbouring miR-133a-3p, predicted decreased cellular functions related to vasculature branching and cell cycle progression, underlining the inhibitory role of miR-133a-3p in angiogenic cellular processes. Our results suggest that controlled delivery of miR-133a-3p mimics, or antagomirs in diseased endothelial cells, might open new therapeutic interventions to treat patients suffering from cardiovascular pathologies that occur with excessive or insufficient angiogenesis.

Citation

Ahmed, S., Kurusamy, S., David, E. L. S., Khan, K., Kalyanakrishnan, K., Ian-Gobo, M., …Armesilla, A. L. (2022). Aberrant expression of miR-133a in endothelial cells inhibits angiogenesis by reducing pro-angiogenic but increasing anti-angiogenic gene expression. Scientific Reports, 12(1), Article 14730. https://doi.org/10.1038/s41598-022-19172-x

Journal Article Type Article
Acceptance Date Aug 25, 2022
Online Publication Date Aug 30, 2022
Publication Date Aug 30, 2022
Deposit Date Nov 10, 2022
Publicly Available Date Mar 29, 2024
Journal Scientific Reports
Electronic ISSN 2045-2322
Peer Reviewed Peer Reviewed
Volume 12
Issue 1
Article Number 14730
DOI https://doi.org/10.1038/s41598-022-19172-x
Keywords Humans; MicroRNAs; Genetics metabolism; Morphogenesis; Transfection; Gene Expression; Endothelial Cells metabolism
Public URL https://nottingham-repository.worktribe.com/output/11462056
Publisher URL https://www.nature.com/articles/s41598-022-19172-x

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