Synchronous profiling of mRNA N6-methyladenosine modifications and mRNA expression in high-grade serous ovarian cancer

Objective: To synchronously determine epitranscriptome-wide RNA N6-methyladenosine (m6A) modifications and mRNA expression profile in high grade serous ovarian cancer (HGSOC). Methods: The methylated RNA immunoprecipitation sequencing (MeRIP-seq) was used to comprehensively examine the m6A modification and the RNA-sequencing (RNA-seq) was performed to analyze the mRNA expression profile in HGSOC and normal fallopian tube (FT) tissues. Go and KEGG analyses were carried out in the enrichment of those differentially methylated and expressed genes. Results: MeRIP-seq data showed 53,794 m6A methylated peaks related to 19,938 genes in the HGSOC group and 51,818 m6A peaks representing 19,681 genes in the FT group. RNA-seq results revealed 2,321 upregulated and 2,486 downregulated genes in HGSOC. Conjoint analysis of MeRIP-seq and RNA-seq data identified differentially expressed genes in which 659 were hypermethylated and 897 were hypomethylated. The expression of the m6A eraser (FTO) was significantly lower, but the m6A readers (IGF2BP2 and IGF2BP3) were higher in HGSOC, which was validated by the subsequent real-time PCR assay. Functional enrichment analysis indicated that these differentially modulated genes are involved in pathways related to cancer development. Conclusions: For the first time, our study screens the epitranscriptome-wide m6A modification and expression profiles of their modulated genes and signaling pathways in HGSOC. Our findings provide an alternative direction in exploring the molecular mechanisms of ovarian pathogenesis.