Li Qinghua, Han Yangyang, Xu Peng, Yin Lingxuan, Si Yanru, Zhang Cuijuan, Meng Yuhan, Feng Weiguo, Pan Zhifang, Gao Zhiqin, Li Jie, Yang Weiwei
1School of Public Health, Weifang Medical University, Weifang, 261053 Shandong China.
2School of Biosciences, Weifang Medical University, Weifang, 261053 Shandong China.
Cell Death Discov. 2020 May 13;6:35. doi: 10.1038/s41420-020-0269-0. eCollection 2020.
Preeclampsia (PE) is a life-threatening disorder of human pregnancy affecting 5-8% of all pregnancies. Currently, PE remains an elusive complicated and heterogenous medical condition with no early marker or symptoms is recognized for this serious pregnancy complications. Here, we profiled the plasma miRNA expression patterns associated with preeclampsia and found 16 miRNAs were deregulated ( < 0.01) in patients who later developed PE. Circulating hsa-miR-125b was aberrantly upregulated in early pregnancy and significantly reduced after delivery in preeclampsia. We then investigated the underlying molecular mechanisms between miR-125b and PE in vitro. We found that upregulated miR-125b can target KCNA1 to inhibit trophoblast invasion in human trophoblast cells. Moreover, overexpression of miR-125b in HUVECs impaired endothelial cell function through GPC1. The findings indicated that upregulated miR-125b leads to impaired placentation, and an increased risk of preeclampsia, Our studies provide novel insights into the underlying mechanisms on the association of miR-125b in early pregnancy and risk of PE, miR-125b might be a more specific predictive marker and a safe therapeutic target for treating patients with PE.
子痫前期(PE)是一种危及生命的人类妊娠疾病,影响着5%至8%的所有妊娠。目前,PE仍然是一种难以捉摸的复杂且异质性的医学病症,对于这种严重的妊娠并发症,尚无早期标志物或症状被识别。在此,我们分析了与子痫前期相关的血浆miRNA表达模式,发现16种miRNA在后来发展为PE的患者中失调(<0.01)。循环中的hsa-miR-125b在子痫前期患者的妊娠早期异常上调,产后显著降低。然后我们在体外研究了miR-125b与PE之间的潜在分子机制。我们发现上调的miR-125b可以靶向KCNA1以抑制人滋养层细胞中的滋养层细胞侵袭。此外,在人脐静脉内皮细胞(HUVECs)中过表达miR-125b会通过GPC1损害内皮细胞功能。这些发现表明上调的miR-125b会导致胎盘形成受损以及子痫前期风险增加。我们的研究为miR-125b在妊娠早期与PE风险关联的潜在机制提供了新的见解,miR-125b可能是一种更特异的预测标志物以及治疗PE患者的安全治疗靶点。