AUTHOR=Nowak-Malczewska Dorota M. , Swierkowska Joanna , Gajecka Marzena 

TITLE=Differentially expressed microRNAs targeting genes in key pathways in keratoconus

JOURNAL=Frontiers in Genetics

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1301676

DOI=10.3389/fgene.2024.1301676

ISSN=1664-8021

ABSTRACT=<p><bold>Introduction:</bold> Keratoconus (KTCN) is a corneal ectasia, characterized by a progressive thinning and protrusion of the cornea, with a complex etiology involving genetic, behavioral, lifestyle, and environmental factors. Previous studies indicated that microRNAs (miRNAs) could be involved in KTCN pathogenesis. This <italic>in silico</italic> study aimed to identify precursor microRNAs (pre-miRNAs) differentially expressed in KTCN corneas and to characterize mature miRNAs and their target genes.</p><p><bold>Materials and methods:</bold> Expression levels of pre-miRNAs were retrieved from our previously obtained RNA sequencing data of 25 KTCN and 25 non-KTCN human corneas (PMID:28145428, PMID:30994860). Differential expression with FDR ≤0.01 and ≥1.5-fold changes were considered significant. Lists of target genes (target score ≥90) of mature miRNAs were obtained from miRDB. Revealed up-/downregulated miRNAs and their target genes were assessed in databases and literature. Enrichment analyses were completed applying the DAVID database.</p><p><bold>Results:</bold> From a total of 47 pre-miRNAs, six were remarkably upregulated (<italic>MIR184</italic>, <italic>MIR548I1</italic>, <italic>MIR200A</italic>, <italic>MIR6728</italic>, <italic>MIR429</italic>, <italic>MIR1299</italic>) and four downregulated (<italic>MIR6081</italic>, <italic>MIR27B</italic>, <italic>MIR23B</italic>, <italic>MIR23A</italic>) in KTCN corneas. Out of the 1,409 target genes, 220 genes with decreased and 57 genes with increased expression levels in KTCN samples vs non-KTCN samples were found. The extracellular matrix (ECM) organization, response to mechanical stimulus, regulation of cell shape, and signal transduction processes/pathways were identified as distinctive in enrichment analyses. Also, processes associated with the regulation of transcription and DNA binding were listed.</p><p><bold>Conclusion:</bold> Indicated miRNAs and their target genes might be involved in KTCN pathogenesis via disruption of crucial molecular processes, including ECM organization and signal transduction.</p>