Association of lncRNA SH3PXD2A-AS1 with preeclampsia and its function in invasion and migration of placental trophoblast cells
Association of lncRNA SH3PXD2A-AS1 with preeclampsia and its function in invasion and migration of placental trophoblast cells
复制标题
lncRNA SH3PXD2A-AS1与子痫前期的关系及其在胎盘滋养层细胞侵袭和迁移中的作用
DOI：
10.1038/s41419-020-02796-0
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发表时间：
2020-07-27
影响因子：
9
通讯作者：
Zhong, Mei
中科院分区：
文献类型：
--
作者：
Chen, Qian;Jiang, Sijia;Zhong, Mei
越来越多的证据表明，子痫前期的发病机制涉及滋养细胞侵袭不足引起的胎盘不良和子宫螺旋动脉重塑受损，但其潜在的分子机制尚不清楚。我们对子痫前期患者和正常受试者的胎盘进行转录组分析，鉴定出约400个长链非编码rna在早发型重度子痫前期患者胎盘中差异表达。在这里，我们报告了我们鉴定的lncRNA SH3PXD2A-AS1是该疾病及其下游途径参与胎盘的潜在致病因素。我们发现SH3PXD2A-AS1在胎盘中的表达水平与患者的临床严重程度呈正相关。我们证明SH3PXD2A- as1通过向SH3PXD2A和CCR7的启动子募集ccctc结合因子（CTCF）来抑制它们的转录，从而抑制了它们的侵袭和迁移。因此，我们得出结论，lncRNA SH3PXD2A-AS1的上调可能通过阻止胎盘滋养细胞侵袭参与子痫前期的发病机制。
Accumulating evidence suggests that the pathogenesis of preeclampsia involves poor placentation caused by insufficient trophoblast invasion and impaired uterine spiral artery remodeling, yet the underlying molecular mechanism remains unclear. We carried out transcriptome profiling on placentae from preeclamptic patients and normal subjects, and identified about four hundred long non-coding RNAs differentially expressed in placentae of patients with early-onset severe preeclampsia. Here, we report our identification of lncRNA SH3PXD2A-AS1 as a potential causal factor for this disease and its downstream pathways involved in placentation. We found that expression level of SH3PXD2A-AS1 in the placentae is positively correlated with clinical severity of the patients. We demonstrated that SH3PXD2A-AS1 inhibited invasion and migration through recruiting CCCTC-binding factor (CTCF) to the promoters of SH3PXD2A and CCR7 to inhibit their transcription. Therefore, we conclude that the upregulation of lncRNA SH3PXD2A-AS1 may contribute to the pathogenesis of preeclampsia through prohibiting trophoblast invasion during placentation.