Wu Haiyan, Zhao Lijuan
Obstetrical Department, Northwest Women's and Children's Hospital, No.1616 Yanxiang Road, Qujiang New District, Xi'an, Shaanxi, 710061, China.
Reprod Sci. 2025 May;32(5):1491-1501. doi: 10.1007/s43032-024-01685-7. Epub 2024 Oct 1.
Circular RNAs (circRNAs) are non-coding RNAs that exert vital function in many human diseases, including preeclampsia (PE). Circ_0015382 is considered to be a key regulator of PE progression, so more molecular mechanisms need to be further studied. Real-time quantitative PCR was used to detect the mRNA levels of circ_0015382, miR-942-5p, and N-myc downstream regulated 1 (NDRG1). Western blot analysis was conducted to assess the protein levels. MTT and EdU assays were used to assess cell proliferation. Cell invasion was analyzed by transwell assay. Tube formation assay was conducted to detect cell angiogenesis. Dual-luciferase reporter assay and RNA immunoprecipitation were used to analyze the target relationship between miR-942-5p and circ_0015382 or NDRG1. Our data showed that circ_0015382 and NDRG1 were up-regulated, while miR-942-5p was down-regulated in the placental tissues of PE patients. Trophoblast cell proliferation, invasion, and angiogenesis were promoted by knockdown of circ_0015382. Circ_0015382 could sponge miR-942-5p, and NDRG1 was a target of miR-942-5p. MiR-942-5p inhibitor could reverse the promoting effects of si-circ_0015382 on trophoblast cell functions. Besides, the enhancing effects of miR-942-5p mimic on trophoblast cell proliferation, invasion, and angiogenesis could be eliminated by NDRG1 overexpression. In conclusion, our data showed that circ_0015382 inhibited trophoblast cell proliferation, invasion, and angiogenesis through regulating miR-942-5p/NDRG1 axis, providing a new mechanism for the regulation of PE progression.
环状RNA(circRNAs)是非编码RNA,在包括先兆子痫(PE)在内的许多人类疾病中发挥着重要作用。Circ_0015382被认为是PE进展的关键调节因子,因此需要进一步研究更多的分子机制。采用实时定量PCR检测circ_0015382、miR-942-5p和N-myc下游调节因子1(NDRG1)的mRNA水平。进行蛋白质免疫印迹分析以评估蛋白质水平。采用MTT和EdU试验评估细胞增殖。通过Transwell试验分析细胞侵袭。进行管形成试验以检测细胞血管生成。采用双荧光素酶报告基因试验和RNA免疫沉淀分析miR-942-5p与circ_0015382或NDRG1之间的靶向关系。我们的数据显示,PE患者胎盘组织中circ_0015382和NDRG1上调,而miR-942-5p下调。敲低circ_0015382可促进滋养层细胞增殖、侵袭和血管生成。Circ_0015382可以吸附miR-942-5p,NDRG1是miR-942-5p的靶标。miR-942-5p抑制剂可逆转si-circ_0015382对滋养层细胞功能的促进作用。此外,NDRG1过表达可消除miR-942-5p模拟物对滋养层细胞增殖、侵袭和血管生成的增强作用。总之,我们的数据表明,circ_0015382通过调节miR-942-5p/NDRG1轴抑制滋养层细胞增殖、侵袭和血管生成,为PE进展的调控提供了新机制。