Methyltransferase-like 3 regulates FOXO1 expression and its effect on decidualization of endometrial stromal cells
10.3760/cma.j.cn101441-20240205-00055
- VernacularTitle:甲基转移酶样蛋白3调控FOXO1的表达及对子宫内膜基质细胞蜕膜化的影响
- Author:
Ting GE
1
;
Manli ZHANG
;
Yunian ZHANG
;
Qiang XU
;
Xiaolin LA
Author Information
1. 新疆医科大学第一附属医院生殖医学中心，乌鲁木齐 830000
- Publication Type:Journal Article
- Keywords:
N6-methyladenosine;
Methyltransferase-like 3;
Decidualization;
Recurrent implantation failure;
Recurrent spontaneous abortion
- From:
Chinese Journal of Reproduction and Contraception
2024;44(11):1146-1155
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the role of methyltransferase-like 3 (METTL3) on endometrial decidualization.Methods:Bioinformatics was used to analyze the expression of 26 N6-methyladenosine (m6A) regulators in recurrent implantation failure (RIF), recurrent spontaneous abortion (RSA) and the decidualization of endometrial stromal cells. Using Medroxyprogesterone and Dibutyryl-cAMP to induce human endometrial stromal cell s (HESCs)decidualization, we examined changes in the expression of total m6A, METTL3, Forkhead framing protein O1 (FOXO1), and decidualization markers insulin-like growth factor binding protein 1 (IGFBP1) and prolactin in the control and decidualization group. Constructing HESC models with METTL3 interference using lentivirus, we used CCK-8 and Edu to detect proliferation in the negative control and knockdown METTL3 group. Lentiviral transfection was successfully followed by induction of decidualization, and we examined changes in the expression of FOXO1 and decidualization markers.Results:The results of bioinformatics analysis showed that the expression of METTL3 was significantly downregulated in the endometrium of patients with RIF and RSA ( P=0.014, P=0.016), while it was significantly upregulated in the endometrium with decidualization ( P=0.029). In vitro, induction of HESCs decidualization increased in the expression levels of total m6A, METTL3, and FOXO1 proteins in the decidualization group ( P=0.015, P=0.016, P=0.004). Knocking down METTL3 resulted in a decrease in FOXO1 protein expression in HESCs ( P=0.009). The CCK-8 and Edu results showed that the proliferation of HESCs was inhibited after knocking down METTL3. After inducing the knockdown of METTL3 in vitro, there was no statistically significant difference in the expression levels of IGFBP1 mRNA, PRL mRNA, and FOXO1 protein in HESCs compared with the negative control group (all P>0.05). Conclusion:In endometrial stromal cells, METTL3 can regulate the expression of FOXO1, promote the expression of IGFBP1 and PRL, and affect the decidualization of endometrial cells.
