Department of Gynecology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou City, China.
J Hypertens. 2024 Jul 1;42(7):1154-1162. doi: 10.1097/HJH.0000000000003692. Epub 2024 Feb 23.
: Circular RNAs (circRNAs) have been shown to be extensively involved in preeclampsia progression. At present, the role of circ_0007445 in preeclampsia progression is not clear.
A total of 30 preeclampsia patients and 30 normal pregnant women were recruited in our study. The function of trophoblast cells was explored to clarify the role and mechanism of circ_0007445 on the preeclampsia progression. The expression of circ_0007445, microRNA (miR)-4432 and high temperature requirement A1 (HTRA1) was analyzed by quantitative real-time PCR. The proliferation, migration and invasion of trophoblast cells were determined by cell counting kit 8 assay, EdU assay, colony formation assay, flow cytometry, and transwell assay. Protein expression was examined by western blot analysis. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull-down assay were used to assess RNA interaction relationships.
Our data suggested that circ_0007445 had increased expression in preeclampsia patients. Knockdown of circ_0007445 enhanced trophoblast cell proliferation, migration and invasion. MiR-4432 was lowly expressed in preeclampsia patients, and it could be sponged by circ_0007445. MiR-4432 inhibitor overturned the promotion effects of circ_0007445 knockdown on trophoblast cell functions. HTRA1 was highly expressed in preeclampsia patients, and it could be targeted by miR-4432. HTRA1 overexpression could also reverse the proliferation, migration and invasion of trophoblast cells promoted by miR-4432 mimic. In addition, circ_0007445 positively regulated HTRA1 through targeting miR-4432.
:Our results suggested that circ_0007445 facilitated the development of preeclampsia by suppressing trophoblast cell function through miR-4432/HTRA1 axis.
环状 RNA（circRNAs）广泛参与子痫前期的进展。目前，circ_0007445 在子痫前期进展中的作用尚不清楚。
本研究共纳入 30 例子痫前期患者和 30 例正常孕妇。通过分析滋养细胞的功能，阐明 circ_0007445 对子痫前期进展的作用和机制。采用实时定量 PCR 分析 circ_0007445、微小 RNA（miR）-4432 和高温需求 A1（HTRA1）的表达。采用细胞计数试剂盒 8 检测、EdU 检测、集落形成检测、流式细胞术和 Transwell 检测分析滋养细胞的增殖、迁移和侵袭。采用 Western blot 分析检测蛋白表达。采用双荧光素酶报告基因检测、RNA 免疫沉淀（RIP）检测和 RNA 下拉检测评估 RNA 相互作用关系。
我们的数据表明，circ_0007445 在子痫前期患者中表达增加。circ_0007445 敲低增强了滋养细胞的增殖、迁移和侵袭。miR-4432 在子痫前期患者中低表达，并且可以被 circ_0007445 海绵吸附。miR-4432 抑制剂逆转了 circ_0007445 敲低对滋养细胞功能的促进作用。HTRA1 在子痫前期患者中高表达，并且可以被 miR-4432 靶向。HTRA1 过表达也可以逆转 miR-4432 模拟物促进的滋养细胞增殖、迁移和侵袭。此外，circ_0007445 通过靶向 miR-4432 正向调节 HTRA1。
我们的结果表明，circ_0007445 通过 miR-4432/HTRA1 轴抑制滋养细胞功能，促进子痫前期的发展。
