The m⁶A methyltransferase METTL3 promotes trophoblast cell invasion by regulating MYLK expression

The progression of placental diseases such as preeclampsia is closely related to trophoblast dysfunction. Recent studies indicated the dysregulation of N6-methyladenosine (m⁶A) RNA modification in trophoblast disorders, while the function of METTL3, a methyltransferase of m⁶A, in trophoblasts remains to be studied.

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.

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.

Collectively, our results highlight an essential role of METTL3-MYLK axis in trophoblast invasion.