Department of Obstetrics and Gynecology, Xijing Hospital,the Military Medical University of PLA Airforce (Fourth Military Medical University), China; Department of Obstetrics, 215 Hospital of Shaanxi Nuclear Industry, China.
Department of Obstetrics and Gynecology, Xijing Hospital,the Military Medical University of PLA Airforce (Fourth Military Medical University), China.
Placenta. 2018 Dec 15;74:1-8. doi: 10.1016/j.placenta.2018.12.003. Epub 2018 Dec 7.
Preeclampsia (PE) is one of the leading causes of maternal and fetal mortality globally. The imbalance of trophoblast homeostasis is closely linked with the pathogenesis of PE. MicroRNA-423-5p (miR-423-5p) has been reported to be abnormally expressed in placenta and blood plasma of pregnant women with PE. In the present study, miR-423-5p expression in blood plasma of pregnant women with PE and healthy pregnant women was detected. Also, the roles and molecular mechanisms of miR-423-5p in the development of trophoblast cells were further investigated.
Expression of miR-423-5p and insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) mRNA was detected by RT-qPCR assay. Protein expression of IGF2BP1, Bcl-2 and Bax was determined using western blot assay. Cell migratory and invasive capacities were assessed by transwell migration and invasion assay. Cell apoptotic rate was determined using flow cytometry via the double-staining of Annexin V-FITC/Propidium Iodide. The interaction between miR-423-5p and IGF2BP1 was demonstrated by bioinformatics analysis and luciferase reporter assay.
MiR-423-5p was highly expressed in blood plasma of pregnant women with PE. MiR-423-5p inhibited migration, invasion and proliferation as well as induced apoptosis in HTR-8/SVneo cells. Further investigation revealed that IGF2BP1 was a target of miR-423-5p. Moreover, IGF2BP1 overexpression promoted migration, invasion and proliferation, suppressed apoptosis, and weakened miR-423-5p function in HTR-8/SVneo cells.
MiR-423-5p inhibited migration, invasion and proliferation as well as induced apoptosis by targeting IGF2BP1 in HTR-8/SVneo cells, presenting a novel molecular basis implicated in PE pathogenesis.
子痫前期（PE）是全球孕产妇和胎儿死亡的主要原因之一。滋养细胞稳态失衡与 PE 的发病机制密切相关。有研究报道，微小 RNA-423-5p（miR-423-5p）在患有 PE 的孕妇胎盘和血浆中表达异常。本研究检测了孕妇血浆中 miR-423-5p 的表达情况，并进一步研究了 miR-423-5p 在滋养细胞发育中的作用及其分子机制。
采用 RT-qPCR 法检测 miR-423-5p 和胰岛素样生长因子 2 mRNA 结合蛋白 1（IGF2BP1）mRNA 的表达，采用 Western blot 法检测 IGF2BP1、Bcl-2 和 Bax 的蛋白表达，采用 Transwell 迁移和侵袭实验检测细胞迁移和侵袭能力，采用流式细胞术双染 Annexin V-FITC/碘化丙啶检测细胞凋亡率，采用生物信息学分析和荧光素酶报告基因实验验证 miR-423-5p 与 IGF2BP1 的相互作用。
PE 孕妇血浆中 miR-423-5p 高表达。miR-423-5p 抑制 HTR-8/SVneo 细胞的迁移、侵袭和增殖，诱导细胞凋亡。进一步研究表明，IGF2BP1 是 miR-423-5p 的靶基因。此外，IGF2BP1 过表达促进 HTR-8/SVneo 细胞的迁移、侵袭和增殖，抑制细胞凋亡，削弱 miR-423-5p 的功能。
miR-423-5p 通过靶向 IGF2BP1 抑制 HTR-8/SVneo 细胞的迁移、侵袭和增殖，诱导细胞凋亡，为 PE 的发病机制提供了新的分子基础。
