| Preeclampsia is a common clinical pregnancy disorder,and the incidence of preeclampsia is about 3 to 5 percent.It is also one of the leading causes of maternal and infant deaths in many areas.The pathogenesis of preeclampsia is not well understood.m6A is the most abundant apparent modification on mRNA and lncRNA,It is highly conservative,regulated by methyltransferases(METTL3,METTL14,WTAP,etc.)and demethylases(ALKBH5,FTO,etc.).m6A is involved in numerous biological processes,and the dysregulation of m6A can cause a variety of diseases including tumors.However,the role of m6A in preeclampsia is unknown.By analyzing RNA sequencing data of placental tissues from normal or patients with preeclampsia,we found that the expression ofALKBH5 gene was up-regulated in the disease samples.Then we verified the increased ALKBH5 protein levels by western blot.During the onset of preeclampsia,hypoxia activates the hypoxia signaling pathway in the placenta and induces the production of HIF1α,and it was reported that ALKBH5 is regulated by hypoxia signaling pathway.Therefore,we use two hypoxia-inducing drugs,DMOG and CoCl2,constructed cell hypoxia model in HTR-8/SVneo cells,and found that ALKBH5 was activated by the HIF1α pathway as expected.We further found that overexpression of ALKBH5 inhibited cell invasion and migration,while knockdown of ALKBH5 enhanced cell invasion and migration.Then,we analyzed the genome-wide m6A on RNA from normal and preeclampsia placenta using Me-RIP-seq,and found the number of m6A peak decreased in preeclampsia samples,and the m6A modified genes was differently distributed in genes associated with placental development,embryo development,and TGFβ signaling pathway.In summary,our research shows that ALKBH5 can affect the invasion and migration ability of placental trophoblast cells through the regulation of m6A modification on RNA,leading to the occurrence of preeclampsia.Therefore,ALKBH5 can be a new potential target for the diagnosis and treatment of preeclampsia. |
PDF Full Text Request