Changzhou Maternity and Child Health Care Hospital affiliated to Nanjing Medical University, Changzhou 213003, Jiangsu, China.
Changzhou Maternity and Child Health Care Hospital affiliated to Nanjing Medical University, Changzhou 213003, Jiangsu, China
Biosci Rep. 2019 Sep 6;39(9). doi: 10.1042/BSR20191965. Print 2019 Sep 30.
Preeclampsia (PE) is the main cause of maternal death in primipara, and commonly results in severe maternal and neonatal complications such as multiple organ dysfunction syndrome. However, the exact pathogenesis of this disease remains unclear. Circular RNAs (circRNAs) are noncoding RNAs that have been shown to be extensively involved in numerous physiological processes, but there is limited knowledge of their functions and mechanisms in PE. In the present study, we found the expression of a circRNA, hsa_circ_0088227 (circRNA of pregnancy-associated plasma protein A, circPAPPA), was down-regulated in both placenta and plasma samples from subjects with PE. Knockdown of circPAPPA led to decreased proliferation and invasion in HTR8-S/Vneo trophoblast cells. miR-384 was identified as a direct target of circPAPPA, and the gene encoding signal transducer and activator of transcription 3 (STAT3) was targeted by miR-384. We found that miR-384 was unregulated in PE, and overexpression of miR-384 could inhibit cell proliferation and invasion. In addition, we showed that the expression of STAT3 was decreased with knockdown of circPAPPA or the overexpression of miR-384 in trophoblast cells, but this decrease was partially reversed when co-transfection was performed with mimics of miR-384 inhibitor and si-circPAPPA. Together, these results suggest that down-regulation of circPAPPA facilitates the onset and development of PE by suppressing trophoblast cells, with involvement of the miR-384/STAT3 signaling pathway. Our study significantly increases the understanding of the occurrence and development of PE, and also provides a molecular target for the treatment of this disorder.
子痫前期 (PE) 是初产妇死亡的主要原因，常导致多器官功能障碍综合征等严重的母婴并发症。然而，这种疾病的确切发病机制尚不清楚。环状 RNA（circRNA）是非编码 RNA，已广泛参与多种生理过程，但对其在 PE 中的功能和机制知之甚少。在本研究中，我们发现环状 RNA hsa_circ_0088227（妊娠相关血浆蛋白 A 的环状 RNA，circPAPPA）在患有 PE 的受试者的胎盘和血浆样本中表达下调。circPAPPA 的敲低导致 HTR8-S/Vneo 滋养细胞增殖和侵袭能力降低。miR-384 被鉴定为 circPAPPA 的直接靶标，而信号转导和转录激活因子 3（STAT3）的基因是 miR-384 的靶标。我们发现 miR-384 在 PE 中上调，过表达 miR-384 可抑制细胞增殖和侵袭。此外，我们表明在滋养细胞中敲低 circPAPPA 或过表达 miR-384 时，STAT3 的表达降低，但当用 miR-384 抑制剂模拟物和 si-circPAPPA 共转染时，这种降低部分得到逆转。总之，这些结果表明下调 circPAPPA 通过抑制滋养细胞促进 PE 的发生和发展，涉及 miR-384/STAT3 信号通路。我们的研究显著增加了对 PE 发生和发展的理解，并为该疾病的治疗提供了分子靶点。
