Signaling roadmap to epithelial–mesenchymal transition in pterygium, TWIST1 centralized

Abstract

Pterygium as a complex disease shares common features with other malignant cells in its onset recurrence and especially epithelial–mesenchymal transition (EMT) transition. Although using different approaches including conjunctival autografts, amniotic membrane, radiotherapy, mitomycin C (MMC) has shown promising insights in the inhibition of pterygium recurrence, it needs to be investigated in more details in molecular pathways to present adjuvant target therapy. In this study, we aimed to evaluate the expression of and then illustrate the role of signaling pathways on EMT in pterygium. Using real‐time polymerase chain reaction, the twist‐related protein 1 (TWIST1) expression was compared in primary pterygium and normal conjunctiva. This study assessed the mRNA expression, as well as the association between the clinicopathological indices and the gene expression level. The expression level of TWIST1 was overexpressed in 36% of our cohort ( n = 76). There was a significant positive correlation between recurrence with grade T, grade V and a significant negative correlation with growth activity. Our vast literature review on different signaling pathways in pterygium showed that EMT has centralization role in recurrence of this disease. Our data confirmed that EMT is important in the recurrence of pterygium samples and different signaling pathways end up activating the EMT markers. It is suggested to evaluate the environmental factors and their correlation with molecular markers to select favorable treatment for this kind of diseases.

A novel role for Livin in the response to ultraviolet�B radiation and pterygium development

“…Knockdown of Livin expression levels increased apoptosis of PECs and decreased their proliferation, migration and invasion abilities, which is consistent with the results of a previous study investigating other IAPs (16). It is hypothesized that EMT occurs during the pathogenesis of pterygium (13). Snail is a key transcription factor involved in EMT regulation (28).…”

“…Snail is a key transcription factor involved in EMT regulation (28). E-cadherin is downregulated in during EMT, associated with the detachment and invasion of cells from their primary site, and results in metastasis and progression (13,28,29). In the present study, Livin-knockdown reduced Snail expression and increased E-cadherin expression, consistent with the reduced proliferation, migration and invasion of PECs following Livin-knockdown, indicating that Livin may be associated with EMT.…”

“…Pterygium is a fibrovascular neoformation composed of epithelium and highly vascular loose subepithelial connective tissue (20). Previous studies have demonstrated that apoptotic and oncogenic proteins, microsatellite instability, inflammatory mediators, extracellular matrix modulators, EMT and other factors are involved in the development of pterygium (4,(9)(10)(11)13). However, to the best of our knowledge, the precise molecular mechanisms of pterygium pathogenesis have not been resolved.…”

“…Pterygium exhibits tumor-like features, including propensity to invade normal tissue, recurrence after excision and coexistence with premalignant lesions (4,7,8). Previous studies have demonstrated that pterygium epithelial cells (PECs) are highly proliferative, have features of epithelial-mesenchymal transition (EMT) and overexpress anti-apoptotic proteins (9)(10)(11)(12)(13). Livin is a member of the inhibitors of apoptosis protein (IAP) family (14), which function in tumor initiation, progression and resistance to chemotherapy (15).…”

MiR‐3175 promotes epithelial‐mesenchymal transition by targeting Smad7 in human conjunctiva and pterygium

“…Recent studies provide evidence that epithelial–mesenchymal transition (EMT) of the epithelial cells may play a key role in the pathogenesis of pterygium . EMT is a fundamental process by which epithelial cells morphologically gradually transform into mesenchymal‐like cells.…”