miRNA and mRNA expression profiling identifies members of the miR-200 family as potential regulators of epithelial–mesenchymal transition in pterygium

Abstract

The current study investigates whether microRNA (miRNA) regulators of epithelial-mesenchymal transition (EMT), tissue fibrosis, and angiogenesis are differentially expressed in human primary pterygium. Genome-wide miRNA and mRNA expression profiling of paired pterygium and normal conjunctiva was performed in the context of conventional excision of pterygium with autotransplantation of conjunctiva (n=8). Quantitative real time polymerase chain reaction (qRT-PCR) was used to validate the expression of key molecules previously detected by microarray. In pterygium, 25 miRNAs and 31 mRNAs were significantly differentially expressed by more than two-fold compared to normal conjunctiva. 14 miRNAs were up-regulated (miR-1246, −486, −451, −3172, −3175, −1308, −1972, −143, −211, −665, −1973, −18a, 143, and −663b), whereas 11 were down-regulated (miR-675, −200b-star, −200a-star, −29b, −200b, −210, −141, −31, −200a, −934, and −375). Unsupervised hierarchical cluster analysis demonstrated that members of the miR-200 family were coexpressed and down-regulated in pterygium. The molecular and cellular functions that were most significant to the miRNA data sets were cellular development, cellular growth and proliferation, and cellular movement. qRT-PCR confirmed the expression of 15 of the 16 genes tested and revealed that miR-429 was down-regulated by more than two-fold in pterygium. The concerted down-regulation of four members from both clusters of the miR-200 family (miR-200a/−200b/−429 and miR-200c/−141), which are known to regulate EMT, and up-regulation of the predicted target and mesenchymal marker fibronectin (FN1), suggest that EMT could potentially play a role in the pathogenesis of pterygium and might constitute promising new targets for therapeutic intervention in pterygium.

MicroRNA-29b Overexpression Decreases Extracellular Matrix mRNA and Protein Production in Human Corneal Endothelial Cells

“…It also has been shown that miR-29 plays a critical role in the pathology of eye diseases, including pterygium 21 , cataract 22 , glaucoma 23–25 and FECD 26 . In trabecular meshwork cells, miR-29 is a critical regulator of ECM expression 23–25 .…”

MicroRNA-215 Regulates Fibroblast Function: Insights from a Human Fibrotic Disease

“…In this hypothesis, epithelial cells transform into abnormal fibroblasts which then mediate the changes that result in pterygium. 35 It is surprising that neither Chien et al 65 nor Engelsvold et al 66 reported miR-215 to be of importance. One reason would be the heterogeneity of tissues involved and the lack of same eye controls in other studies.…”

Impact of Altered WNT2B Expression on Bladder Wall Fibroblasts: Implications for Apoptosis Regulation in the Stroma of the Lower Urinary Tract

“…This microRNA has not been described in the context of tissue fibrosis. Yet, other studies found it to be associated with EMT processes [31]. It has also been described to be associated with stemness and invasiveness of non-small cell lung cancer [32].…”