MicroRNA regulation of MDM2-p53 loop in pterygium.

ABSTRACT

PURPOSE: The pathogenesis of pterygium has been linked to limbal stem cell damage, abnormal apoptosis and cellular proliferation. In this study, we investigated the epigenetic regulation through microRNA expression in the pathogenesis of pterygium. METHODS: Human full-length primary pterygia were microdissected into head and body regions. Specific microRNA and mRNA expression was assayed by TaqMan® real-time quantitative polymerase chain reaction (qPCR). Tissue localization of target microRNAs was performed by LNA-based in situ hybridization. MicroRNA-145 (miR-145) mimics were transfected to primary culture of human pterygial cells, followed by analyses of cell cycle changes, apoptosis, p53 and MDM2 expression using flow cytometry and qPCR. RESULTS: The expression of miR-145 was markedly higher in primary human pterygium than in limbus and conjunctiva. Both miR-143 and miR-145 were predominantly expressed in the basal pterygial epithelium. Oncogene MDM2 expression was abundant in pterygial epithelium and stroma, while the expression pattern was opposite to that of miR-145. Ectopic expression of miR-145 in pterygial cells induced G1 arrest, down-regulated MDM2 and elevated p53 expression. CONCLUSIONS: Our study showed that miR-145 suppressed MDM2 expression, which subsequently influenced the p53-related cell growth pattern in pterygial epithelium. The regulatory miR-145/MDM2-p53 loop can serve as a potential target for treatment of pterygium.