Dysregulated expressions of miR-3074-5p and its target gene p27 in placenta of pre-eclampsia patients
10.3760/cma.j.cn101441-20200825-00460
- VernacularTitle:miR-3074-5p及其靶基因 p27在子痫前期胎盘组织中的异常表达
- Author:
Yan GU
1
;
Lei QIAO
;
Zhuoran FAN
;
Wenwen GU
;
Hongna SHENG
;
Jianmei WANG
;
Shaofang HUA
;
Xuan ZHANG
Author Information
1. 天津医科大学第二医院 300221
- Publication Type:Journal Article
- Keywords:
miR-3074-5p;
p27;
Preeclampsia;
Placenta;
Trophoblast cell
- From:
Chinese Journal of Reproduction and Contraception
2021;41(9):812-821
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To detect the expression levels of miR-3074-5p and its target gene p27 in the placental tissues of pre-eclampsia (PE) patients, and to preliminarily explore the association of miR-3074-5p/p27 pathway in the pathogenesis of PE. Methods:From September 2017 to March 2018, 16 pregnant women with PE (PE group) and 9 normal pregnant women (control group) were enrolled in Obstetrics Department in the Second Hospital of Tianjin Medical University. The placental expression levels of miR-3074-5p, p27, cyclin D1 (CCND1) and cyclin dependent kinase 2 (CDK2) were determined by quantitative PCR (qPCR), Western blotting and immunohistochemistry (IHC) analyses. The dual-luciferase reporter assay was applied to authenticate the directly targeted effect of miR-3074-5p on expression of p27 mRNA. The expression of p27 in the human extravillous trophoblast cell line HTR-8/SVneo was down-regulated by its specific shRNA, and the effects of down-regulated p27 expression on physiological activities of HTR-8/SVneo cells were detected. Results:Compared with control group, the expression levels of miR-3074-5p ( P=0.034) and CCND1 ( P=0.031) protein in the placenta of PE patients were significantly decreased, whereas the placental p27 ( P=0.010) protein expression was significantly increased in PE group. IHC analysis showed that, the signals of p27 and CCND1 proteins were dominantly detected in syncytiotrophoblast. The results of dual-luciferase reporter assay confirmed that miR-3074-5p could inhibit the expression of p27 by directly bound to the 3'UTR of p27 mRNA. After the p27 expression was down-regulated, the proliferative and invasive activities of HTR-8/SVneo cells were significantly enhanced ( P=0.014, P=0.045). Conclusion:miR-3074-5p might participate in the regulation of physiological activities of extravillous trophoblast cells by its targeted inhibition on p27 expression, and the abnormally decreased miR-3074-5p in trophoblast cells might be associated with the pathogenesis of PE by promoting the expression of p27.
