Discussion
Collectively, our results highlight an essential role of METTL3-MYLK axis in trophoblast invasion.
Methods
The expression of METTL3 was determined by real-time PCR and immunoblotting. METTL3 expression in trophoblast cell lines HTR-8/SVneo and JEG-3 was knocked down using shRNA. The invasion of trophoblast cells in Matrigel was determined using xCELLigence. The m6A-containing transcripts was determined by m6A-sequencing in HTR-8/SVneo cells. The myosin light chain kinase (MYLK) gene was transfected into HTR-8/SVneo cells.
Results
The expression of METTL3 was downregulated in preeclamptic placentae compared to normal placentae. Knockdown of METTL3 repressed the invasion of extravillous trophoblast cells. Mechanistically, METTL3 promoted the stability of MYLK mRNA through m6A modification. Overexpression of MYLK rescued retarded cell invasion by METTL3 depletion.