Department of Obstetrics, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China.
J Obstet Gynaecol Res. 2022 Jul;48(7):1698-1709. doi: 10.1111/jog.15297. Epub 2022 May 29.
Circular RNA plays a critical role in cell proliferation, differentiation, and autophagy. However, the role and mechanism of circRNA in preeclampsia is yet to be clarified. The present study investigated the function and mechanism of circ-0002814 in preeclampsia.
The expression level of circ-0002814, microRNA 210 (miR210), Notch receptor 1 (Notch1), or cytoplasmic polyadenylation element-binding protein 2 (CPEB2) was investigated by Reverse transcription Real-time Quantitative PCR (RT-qPCR). The level of Notch1, CPEB2, and FUS (FUS RNA-binding protein) proteins was detected by western blot. The localization of circ-0002814 and miR-210 was determined by FISH assay. Cell proliferation and invasion were detected by EdU and transwell assays, respectively. The interaction between circ-0002814 and FUS protein was detected by RNA pulldown assay, while that between circ-0002814 and miR-210 was detected by dual-luciferase reporter assay.
The expression of circ-0002814 was decreased in the placenta and plasma of patients with preeclampsia. The ectopic expression of circ-0002814 promoted the invasion and proliferation of HTR8 cells compared to the control group (p < 0.05). Silencing circ-0002814 suppressed the invasion and proliferation of JEG3 cells compared to the control group (p < 0.05). circ_0002814-regulated Notch1 and CPEB2 by interaction with miR-210 and also regulated FUS/VEGF axis in HTR8 and JEG3 cells.
A low expression of circ-0002814 was detected in the plasma and placental tissue in preeclampsia patients. circ-0002814 participated in the proliferation and invasion of HTR8 and JEG3 cells. Thus, circ-0002814 may be considered as a potential diagnostic marker and therapeutic target for preeclampsia.
环状 RNA 在细胞增殖、分化和自噬中发挥着关键作用。然而，环状 RNA 在子痫前期中的作用和机制尚不清楚。本研究旨在探讨环状 RNA circ-0002814 在子痫前期中的功能和机制。
采用逆转录实时定量 PCR（RT-qPCR）检测 circ-0002814、微小 RNA 210（miR210）、Notch 受体 1（Notch1）或细胞质多聚腺苷酸化元件结合蛋白 2（CPEB2）的表达水平。采用 Western blot 检测 Notch1、CPEB2 和 FUS（FUS RNA 结合蛋白）蛋白的水平。采用荧光原位杂交（FISH）检测 circ-0002814 和 miR-210 的定位。采用 EdU 和 Transwell 检测细胞增殖和侵袭。采用 RNA 下拉实验检测 circ-0002814 与 FUS 蛋白的相互作用，采用双荧光素酶报告基因实验检测 circ-0002814 与 miR-210 的相互作用。
子痫前期患者胎盘和血浆中 circ-0002814 的表达降低。与对照组相比，外源性表达 circ-0002814 可促进 HTR8 细胞的侵袭和增殖（p<0.05）。与对照组相比，沉默 circ-0002814 可抑制 JEG3 细胞的侵袭和增殖（p<0.05）。circ_0002814 通过与 miR-210 相互作用调控 Notch1 和 CPEB2，还可调控 HTR8 和 JEG3 细胞中的 FUS/VEGF 轴。
子痫前期患者血浆和胎盘组织中 circ-0002814 表达降低。circ-0002814 参与 HTR8 和 JEG3 细胞的增殖和侵袭。因此，circ-0002814 可作为子痫前期的潜在诊断标志物和治疗靶点。
