MicroRNAs (miRNAs) play critical roles in ocular surface diseases. In our recent study, through microarray analysis, miR-138-5p was identified as one of the most prominent miRNAs expressed in aniridia patients derived primary limbal epithelial cells (pLECs). Although miR-138-5p expression was significantly elevated in aniridia samples, its specific role in the pathogenesis of aniridia-associated keratopathy (AAK) remained unclear. Therefore, the present study focused on exploring the potential functional impact of upregulated miR-138-5p on limbal epithelial stem cell maintenance and function. Cultured pLECs of healthy human donors isolated from corneoscleral rims were transfected with miR-138-5p mimics. The gene and protein expression level of direct target genes of miR138-5p were evaluated. Additionally, cell proliferation, apoptosis, and cell cycle progression was assessed. Overexpression of miR-138-5p significantly downregulated the expression of several target genes, including Cyclin D (CCND1 and CCND3), Hypoxia-Inducible Factor 1-alpha (HIF1A), Forkhead Box C1 (FOXC1), Caspase 3 (CASP3) , and Fos-like 1 (FOSL1) . Protein levels of Cyclin D1 were also significantly reduced. Additionally, miR-138-5p transfection markedly inhibited cell proliferation and cell cycle progression. Our results demonstrate that miR138-5p can regulate CCND1 expression, and that its overexpression inhibits limbal epithelial cell proliferation and induces cell cycle arrest, suggesting that miR-138-5p acts as a negative regulator in limbal epithelial cells. Therefore, identifying strategies to suppress miR-138-5p expression at the ocular surface in congenital aniridia could have therapeutic potential for slowing the progression of AAK. Nonetheless, further in vivo studies are needed to fully elucidate the mechanistic link between miR-138-5p and AAK pathogenesis. • This study explores the in vitro functional role of miR-138-5p, a microRNA found to be upregulated in primary limbal epithelial cells derived from aniridia patient biopsies. • Overexpression of miR-138-5p in healthy primary limbal epithelial cells downregulates mRNA expression of Cyclin D1/D3, HIF-1α, FOXC1, Caspase-3 , and FOSL1. • miR-138-5p inhibits limbal epithelial cell proliferation and induces cell-cycle arrest in vitro.
Suiwal et al. (Sun,) studied this question.