Found programs: National Natural Science Foundation of China (Nos . 81960080 , 81760069)
Authors:Tang Xiong , Chen Fan , Xie Siyu , Guo Yafei , He Ye , Zhang Ying
Keywords:myocardial infarction; C1q tumor necrosis factor-related protein 3 ; SeVGMT; reprogramming; cardi- ac fibroblasts; ubiquitin carboxyl-terminal hydrolase L1
DOI:10.19405/j.cnki.issn1000-1492.2025.10.015
〔Abstract〕 To explore the role of N6-methyladenosine ( m6A) modification of RNA and Methyltrans- ferase like Protein 14 methyltransferase (METTL14) in the pathogenesis of early-onset preeclampsia (ePE) . Meth- ods Placental tissues of 15 pregnant women with early-onset preeclampsia and 15 normal pregnant women were collected . The level of m6A was determined by colorimetry , and the expression of METTL14 was determined by RT-qPCR , Western blot and immunohistochemistry ( IHC ) experiments . By transfecting siRNA and plasmid , METTL14 levels of trophoblast cells were knocked down and overexpressed , and cell phenotype experiments were carried out in vitro . The effects of METTL14 on the proliferation , migration and invasion of trophoblast cells were investigated by CCK-8 , scratch assay , Transwell assay and invasion assay . Results The level of m6A in placental tissue of ePE was lower than that of normal pregnancy . METTL14 was mainly expressed in the nuclei of trophoblast cells . Compared with normal pregnancy , the expression of METTL14 in placental tissue of ePE decreased , and the level of METTL14 mRNA was positively correlated with the level of m6A in placental tissue . The results of the CCK-8 experiment showed that compared with the control group , knockdown of METTL14 expression in trophoblast cells significantly reduced the cell proliferation rate , while the proliferation ability of trophoblast cells with overex- pressed METTL14 was enhanced . The results of the scratch test showed that compared with the control group , the relative healing rate of scratches was significantly reduced after METTL14 knockdown , while it increased after the overexpression of METTL14 . The results of the Transwell assay and invasion assay showed that compared with the control group , after knockdown of METTL14 , the number of trophoblast cells passing through the chamber was sig- nificantly reduced , while the number of trophoblast cells with overexpressed METTL14 passing through the chamber increased . Conclusion The total RNA m6A modification level in placental tissue of ePE is lower than that in the normal pregnancy group . The down-regulation of methyltransferase METTL14 is involved in the regulation of the to- tal RNA m6A modification level . The overexpression of METTL14 can enhance the proliferation , migration and in- vasion abilities of trophoblast cells . It provides a new perspective for exploring the pathogenesis of early-onset pre- eclampsia.