GSE137675
Analysis of gene expression, motif and pattern of m6A modified region and m6A enrichment level in Ocular melanoma and Melanocyte cell lines. Gene expressin analysis of METTL3 knock down in PIG1, ALKBH5 knock down and HINT2 over expression in OCM1.
Dynamic N6-methyladenosine (m6A) RNA modification installed and erased by N6-methyltransferases and demethylases regulates gene expression, alternative splicing and cell fate. Ocular melanoma, comprising uveal melanoma (UM) and conjunctival melanoma (CM), is the most common primary eye tumor in adults and the 2nd most common melanoma. However, the functional role of m6A modification in ocular melanoma remains unclear. Here, we show that RNA methylation significantly inhibits the progression of uveal melanoma and conjunctival melanoma. Ocular melanoma samples showed decreased m6A levels, indicating a poor prognosis. Changes in global m6A modification were highly associated with tumor progression in vitro and in vivo. Mechanistically, YTHDF1 promoted the translation of methylated HINT2 mRNA, a tumor suppressor in ocular melanoma. Our work uncovers a critical function for m6A methylation in ocular melanoma and provides additional insight into the understanding of m6A modification. Overall design: RNA-seq, miCLIP-seq and MeRIP-seq for five Ocular melanoma cell lines (CM2005.1, CRMM1, OCM1, OCM1a and OM431) and one Melanocyte cell line (PIG1).