Guo Linqiong, Ji Ting, Xu Xiaoyan, Liu Xing, Cui Yanping
Department of Obstetrics, Northwest Women's and Children's Hospital, 1616 Yanxiang Road, Qujiang New District, Xi'an, 710061, China.
Reprod Sci. 2025 May;32(5):1600-1611. doi: 10.1007/s43032-024-01757-8. Epub 2024 Dec 11.
Preeclampsia (PE), an idiopathic hypertensive disorder that arises during pregnancy, poses a serious threat to the health of expectant mothers. Human chorionic trophoblast cells (HTR-8/SVneo) are associated with the development of PE. It has been reported that circ_0008440 expression is abnormally increased in the placental tissues of PE patients. However, the function of circ_0008440 within HTR-8/SVneo cells during PE has yet to be fully elucidated. The study used RT-qPCR and western blot assay to evaluate the expression levels of 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 2 (PFKFB2), circ_0008440, and miR-942-5p in PE patients. Cells viability was measured using cell counting kit-8 (CCK-8) assay. Cell cycle assay and 5-ethynyl-2'-deoxyuridine (EDU) assay were used to measure cell proliferation. Cell apoptosis was assessed using flow cytometry assay. Western blot assay was used to detect protein expression. Dual-luciferase reporter assay and RNA pull-down assay were used to assess the interactions among circ_0008440, miR-942-5p, and PFKFB2 in HTR-8/SVneo cells. The study showed that the expression levels of circ_0008440 and PFKFB2 were significantly increased, while the expression of miR-942-5p was significantly decreased in the placental tissues of PE patients. Silencing of circ_0008440 promoted proliferation and tube formation and inhibited apoptosis of HTR-8/SVneo cells. In terms of molecular mechanism, miR-942-5p inhibitor or overexpression of PFKFB2 could partially reverse the effects of circ_0008440 silencing on the biological characteristics of HTR-8/SVneo cells. Collectively, circ_0008440 could act as a sponge of miR-942-5p to regulate the expression of PFKFB2, which further inhibited viability and proliferation of HTR-8/SVneo cells and promoted cell apoptosis.
子痫前期（PE）是一种在孕期出现的特发性高血压疾病，对孕妇的健康构成严重威胁。人绒毛膜滋养层细胞（HTR-8/SVneo）与子痫前期的发生发展有关。据报道，circ_0008440在子痫前期患者胎盘组织中的表达异常增加。然而，子痫前期期间circ_0008440在HTR-8/SVneo细胞中的功能尚未完全阐明。该研究采用RT-qPCR和蛋白质免疫印迹法评估子痫前期患者中6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶2（PFKFB2）、circ_0008440和miR-942-5p的表达水平。使用细胞计数试剂盒-8（CCK-8）检测细胞活力。采用细胞周期检测和5-乙炔基-2'-脱氧尿苷（EDU）检测来测定细胞增殖。使用流式细胞术检测细胞凋亡。采用蛋白质免疫印迹法检测蛋白质表达。采用双荧光素酶报告基因检测和RNA下拉检测来评估circ_0008440、miR-942-5p和PFKFB2在HTR-8/SVneo细胞中的相互作用。研究表明，子痫前期患者胎盘组织中circ_0008440和PFKFB2的表达水平显著升高，而miR-942-5p的表达显著降低。circ_0008440沉默促进了HTR-8/SVneo细胞的增殖和管腔形成，并抑制了细胞凋亡。在分子机制方面，miR-942-5p抑制剂或PFKFB2过表达可部分逆转circ_0008440沉默对HTR-8/SVneo细胞生物学特性的影响。总的来说，circ_0008440可作为miR-942-5p的海绵来调节PFKFB2的表达，进而抑制HTR-8/SVneo细胞的活力和增殖并促进细胞凋亡。
