Department of Obstetrics, Jinan Maternal and Child Health Hospital, Shandong, China.
Department of Outpatient, Jinan Maternal and Child Health Hospital, Shandong, China.
Placenta. 2021 Jan 15;104:40-50. doi: 10.1016/j.placenta.2020.11.005. Epub 2020 Nov 18.
Preeclampsia (PE) is a common pregnancy disorder with multisystem complications. The growing data suggest that circular RNAs (circRNAs) involve in the development of PE. This study proposed to investigate the function and potential mechanisms of circ_0001438 in PE.
The expression of circ_0001438, miR-942 and NOD-like receptor pyrin domain-containing protein 3 (NLRP3) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The expression at the protein level of NLRP3, interleukin 1 beta (IL-1β), interleukin 10 (IL-10), B-cell lymphoma 2 (Bcl-2), Cleaved-caspase-3 (Cleaved-casp-3), N-cadherin and E-cadherin was detected by Western blot. Cell proliferation was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and colony formation assay. Cell apoptosis was determined by flow cytometry assay. Cell migration and invasion were monitored by transwell assay. The target genes were obtained and verified by the online bioinformatics tool and dual-luciferase reporter assay.
The expression of circ_0001438 and NLRP3 was enhanced in PE placenta tissues. Circ_0001438 knockdown promoted cell proliferation, migration and invasion but inhibited apoptosis and inflammatory responses in HTR-8/Svneo cells, and these effects were reversed by the inhibition of miR-942, a target of circ_0001438. Moreover, NLRP3 was bounded by miR-942. The enrichment of miR-942 accelerated cell proliferation, migration and invasion but depleted apoptosis and inflammatory responses, while these impacts were partly abolished by NLRP3 overexpression.
Circ_0001438 sponged miR-942 to regulate the expression of NLRP3, and circ_0001438 aggravated the dysfunctions of human villous trophoblasts by mediating the miR-942/NLRP3 axis at least in part.
子痫前期（PE）是一种常见的妊娠并发症，伴有多系统并发症。越来越多的数据表明，环状 RNA（circRNA）参与了 PE 的发生发展。本研究旨在探讨 circ_0001438 在 PE 中的作用及潜在机制。
采用实时定量聚合酶链反应（qRT-PCR）检测 circ_0001438、miR-942 和 NOD 样受体含 pyrin 结构域蛋白 3（NLRP3）的表达。采用 Western blot 检测 NLRP3、白细胞介素 1β（IL-1β）、白细胞介素 10（IL-10）、B 细胞淋巴瘤 2（Bcl-2）、Cleaved-caspase-3（Cleaved-casp-3）、N-钙黏蛋白和 E-钙黏蛋白的蛋白水平表达。采用 3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐（MTT）法和集落形成实验检测细胞增殖。采用流式细胞术检测细胞凋亡。通过 Transwell 实验监测细胞迁移和侵袭。利用在线生物信息学工具和双荧光素酶报告基因实验获得并验证靶基因。
PE 胎盘组织中 circ_0001438 和 NLRP3 的表达增加。circ_0001438 敲低促进 HTR-8/Svneo 细胞增殖、迁移和侵袭，但抑制细胞凋亡和炎症反应，而这些作用可被 circ_0001438 的靶基因 miR-942 的抑制所逆转。此外，miR-942 与 NLRP3 结合。miR-942 的富集加速了细胞增殖、迁移和侵袭，但减少了细胞凋亡和炎症反应，而这些影响部分被 NLRP3 的过表达所消除。
circ_0001438 通过海绵吸附 miR-942 来调节 NLRP3 的表达，circ_0001438 通过介导 miR-942/NLRP3 轴至少部分加重了人绒毛滋养层细胞的功能障碍。
