The mRNA m6A reader YTHDF2 suppresses the proliferation and migration of pterygium fibroblasts

Abstract BACKGROUND: Pterygium is a common, benign ocular surface disease. Its characteristics, such as hyper-proliferation, anti-apoptotic behavior, and high recurrence rate, contribute to the tumourigenic-like features. Emerging evidence has shown that N6-methyladenosine (m6A) modification plays a vital role in pterygium progression. YTHDF2, an m6A reader, is recognized as promoting targeted mRNA decay. However, the effect of YTHDF2 on pterygium fibroblasts is unknown and remains to be elucidated. METHODS: 42 pterygium tissues and 42 conjunctiva tissues were obtained from pterygium patients who were recruited from the 2nd Xiangya Hospital. The level of m6A modification was detected using an m6A RNA Methylation Quantification Kit. Quantitative real-time PCR (qRT-PCR) compared the differential expression among binding proteins, methyltransferases, and demethylases. The expression and location of YTHDF2 were identified by immunofluorescence. Plasmid construction, Cell transfection, Western blotting, Cell Counting Kit-8 (CCK-8), and Scratch Wound Healing Assay were used to evaluate the effect of YTHDF2 on proliferation and migration of cultured human pterygium fibroblasts (HPFs). RESULTS: Our research demonstrated that YTHDF2 expression was decreased in HPFs, and overexpression of YTHDF2 could inhibit the proliferation and migration of HPFs. Global m6A expression levels were related to the expression of multiple m6A-related proteins. CONCLUSIONS: Our study indicated that YTHDF2 might act as a suppressor to suppress the proliferation and migration of fibroblasts in pterygium. This finding provides additional insight into understanding the role of m6A modification in pterygium.