Roodnat, Anton W, Doyle, Chelsey, Callaghan, Breedge, Lester, Karen, Henry, Megan, Sheridan, Carl 
ORCID: 0000-0003-0100-9587, Mckenna, Declan J, Willoughby, Colin E and Atkinson, Sarah D
(2025)
Investigating the miRNA-mRNA interactome of human trabecular meshwork cells treated with TGF-β1 provides insights into the pathogenesis of pseudoexfoliation glaucoma
PLOS ONE, 20 (1).
e0318125-.
ISSN 1932-6203, 1932-6203
Abstract
Pseudoexfoliation glaucoma is a severe form of secondary open angle glaucoma and is associated with activation of the TGF-β pathway by TGF-β1. MicroRNAs (miRNAs) are small non-coding RNA species that are involved in regulation of mRNA expression and translation. To investigate what glaucomatous changes occur in the trabecular meshwork and how these changes may be regulated by miRNAs, we performed a bioinformatics analysis resulting in a miRNA-mRNA interactome. Primary human trabecular meshwork cells originating from normal donors were treated with TGF-β1 at 5 ng/mL for 24h; total RNA was extracted followed by RNA-Seq and miRNA-Seq. For both mRNA and miRNA species, differential expression was determined using a bioinformatics pipeline consisting of FastQC, STAR, FeatureCounts, edgeR (for miRNA) and DESeq2 (for mRNA). Putative mRNAmiRNA interactions between differentially expressed mRNA and miRNA species were determined using interaction databases miRWalk, miRTarBase, TarBase and TargetScan. To classify mRNA species by function and pathway, gene enrichment was performed using Enrichr. The resulting miRNA-mRNA interactome consisted of 1202 interactions. Some highly connected microRNAs were hsa-let-7e-5p, hsa-miR-20a-5p, hsa-miR-122-5p, and hsa-miR-29c-3p. Most differentially expressed genes were indicated to be regulated by miRNAs. The sub-interactomes of genes involved in specific pseudoexfoliation glaucoma related enrichment terms such as oxidative stress, unfolded protein response, signal molecules and ECM remodelling were determined. This is the first study to present a genomewide microRNA-mRNA regulatory network for human trabecular meshwork cells treated with TGF-β1 and may serve to generate unbiased hypotheses about regulatory functions and mRNA targets of miRNAs in pseudoexfoliation glaucoma and may help to develop miRNA-based therapeutics.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Trabecular Meshwork, Cells, Cultured, Humans, Glaucoma, Open-Angle, Exfoliation Syndrome, MicroRNAs, RNA, Messenger, Gene Expression Profiling, Computational Biology, Gene Expression Regulation, Transforming Growth Factor beta1, Gene Regulatory Networks |
| Divisions: | Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 26 Mar 2025 10:42 |
| Last Modified: | 16 Jun 2026 20:13 |
| DOI: | 10.1371/journal.pone.0318125 |
| Open Access URL: | https://doi.org/10.1371/journal.pone.0318125 |
| Related Websites: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3191038 |
| Disclaimer: | The University of Liverpool is not responsible for content contained on other websites from links within repository metadata. Please contact us if you notice anything that appears incorrect or inappropriate. |
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