Fig. 9
The schematic of molecular mechanism about how METTL3 affected TMBIM6 expression resulting in trophoblastic dysfunction and PE. ①When placentas got injured by many detrimental factors, such as I/R, the trophoblasts were under ER stress and METTL3 expression was upregulated increasing the m6A modification of TMBIM6 mRNA in trophoblasts. ② The methylated TMBIM6 mRNA was recognized by YTHDF2. ③ YTHDF2 decreased the stability of TMBIM6 mRNA and increased its degradation. ④ TMBIM6 expression was downregulated due to the decreased TMBIM6 mRNA and its translation. ⑤ Downregulation of TMBIM6 could not maintain the ER homeostasis, which aggravated ER stress. Moreover, the apoptosis and ROS production were increased when TMBIM6 was decreased. ⑥ The trophoblasts functions were impaired with the placental functions abnormal, which consequently contributed to PE