m6A mRNA methylation regulates the development of gestational diabetes mellitus in Han Chinese women.

N6-methyladenosine (m6A) is the most prevalent mRNA modification in mammals. However, m6A modification profiling and its potential role in gestational diabetes mellitus (GDM) have not yet been investigated. In this work, we performed comprehensive m6A analysis in placental tissues from GDM and control patients to elucidate the role of m6A in GDM. An m6A RNA profile identified that m6A levels were strongly decreased in 3'-untranslated regions (UTRs) and coding sequences (CDSs) near stop codons in GDM placenta samples. Among the many methylated mRNAs, MazF-qPCR verified that the m6A levels of the BAMBI 3'-UTR and CDS were significantly decreased in GDM. BAMBI mRNA and protein expression was significantly decreased in GDM, suggesting that m6A plays a key role in regulating gene expression. In addition, it was verified that the m6A levels of GDM related genes (INSR and IRS1) were significantly reduced in GDM. Taken together, our data suggest that down-regulation of m6A both in the 3'-UTR and CDS near stop codons of placental mRNAs is involved in GDM development in Han Chinese women.