Reproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, Hubei, 430060, PR China.
Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, PR China.
Placenta. 2022 Feb;118:20-31. doi: 10.1016/j.placenta.2022.01.001. Epub 2022 Jan 5.
Recurrent miscarriage (RM), refers to two or more consecutive spontaneous miscarriage in a pregnant woman. RM is caused by many factors, and microRNAs play an important role in the development and pathology of RM. In the present study, we investigated the function of miR-187 in the pathogenesis of RM and its effects on human trophoblast cells.
The localization of miR-187 in the human placenta in early pregnancy was determined by in situ hybridization. QRT-PCR was used to detect the expression of miR-187 in villi of normal early pregnancy induced abortion group and recurrent spontaneous miscarriage group. Then, HTR8/SVneo cells were used to investigated the effect of miR-187 on BCL6 expression and biological activity of trophoblasts.
We found that the expression of miR-187 in villi of RM group was higher than that of normal abortion group and miR-187 inhibited the proliferation, migration, and invasion of HTR8 cells. We also found that miR-187 promoted apoptosis, inhibited EMT, and inhibited the PI3K/AKT pathway in HTR8 cells. In addition, we also found that BCL6 is a direct target of miR-187 and is negatively regulated by miR-187. In addition, BCL6 reversed the inhibitory effects of miR-187 on HTR8/SVneo cells. These data demonstrate that miR-187-induced repression of PI3K/AKT signaling is mediated by BCL6 in HTR8 cells.
MiR-187 inhibits the proliferation, migration, and invasion of trophoblasts through a mechanism that involves regulation of BCL6.
复发性流产(RM)是指孕妇连续两次或两次以上自然流产。RM 由多种因素引起,microRNAs 在 RM 的发生发展和病理过程中起重要作用。本研究探讨了 miR-187 在 RM 发病机制中的作用及其对人滋养层细胞的影响。
通过原位杂交确定 miR-187 在人早孕胎盘组织中的定位。采用 QRT-PCR 检测正常早孕流产组和复发性自然流产组绒毛中 miR-187 的表达。然后,用 HTR8/SVneo 细胞研究 miR-187 对 BCL6 表达和滋养层细胞生物学活性的影响。
我们发现 RM 组绒毛中 miR-187 的表达高于正常流产组,miR-187 抑制 HTR8 细胞的增殖、迁移和侵袭。我们还发现 miR-187 促进 HTR8 细胞凋亡,抑制 EMT,抑制 PI3K/AKT 通路。此外,我们还发现 BCL6 是 miR-187 的直接靶标,并受 miR-187 的负调控。此外,BCL6 逆转了 miR-187 对 HTR8/SVneo 细胞的抑制作用。这些数据表明,miR-187 通过抑制 BCL6 抑制 PI3K/AKT 信号通路。
miR-187 通过调节 BCL6 抑制滋养层细胞的增殖、迁移和侵袭。