Department of Obstetrics and Gynecology, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, China.
Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, People's Republic of China.
Funct Integr Genomics. 2024 Nov 5;24(6):208. doi: 10.1007/s10142-024-01490-0.
Preeclampsia (PE) is a severe pregnancy complication linked to maternal and fetal health, yet its underlying causes and pathogenesis remain elusive. Circular RNA (circRNA), a form of non-coding RNA, is implicated in the progression of PE; nevertheless, the specific mechanism is not fully elucidated. This study aimed to identify and validate circRNAs that are pivotal in the pathophysiology of PE. Firstly, we constructed a ceRNA network using datasets from the GEO database and identified circ_0022707 as our study target. Then, using qRT-PCR analysis, we validated that circ_0022707 was downregulated in preeclamptic placentas compared to those of normal pregnant women. In situ hybridization assays revealed that circ_0022707 existed in placental villous trophoblast cells. Additionally, Pearson correlation analysis revealed a negative relationship between the expression of circ_0022707 and PE-related indicators (systolic and diastolic blood pressure, along with 24-h proteinuria levels). Furthermore, gain-of-function experiments confirmed that circ_0022707 could promote trophoblast cell proliferation and cell cycle progression while suppressing apoptosis. In vivo experiments using a preeclampsia-like mouse model also demonstrated that circ_0022707 administration could mitigate preeclampsia-like symptoms. Mechanistically, we confirmed that circ_0022707 functions through the miR-3135b/GHR/PI3K/Akt pathway in trophoblast cells. Overall, our study has provided insight into the important function of circ_002707 in the development of PE, enhancing our understanding of the disease's mechanism and proposing a viable therapeutic strategy for PE.
子痫前期 (PE) 是一种与母婴健康相关的严重妊娠并发症，但其潜在病因和发病机制仍不清楚。环状 RNA (circRNA) 作为一种非编码 RNA，与 PE 的进展有关；然而，其具体机制尚未完全阐明。本研究旨在鉴定和验证在 PE 病理生理学中起关键作用的 circRNA。首先，我们使用 GEO 数据库中的数据集构建了 ceRNA 网络，并将 circ_0022707 确定为我们的研究目标。然后，通过 qRT-PCR 分析，我们验证了 circ_0022707 在子痫前期胎盘组织中较正常妊娠妇女的胎盘组织呈下调表达。原位杂交检测显示 circ_0022707 存在于胎盘绒毛滋养细胞中。此外，Pearson 相关分析显示 circ_0022707 的表达与 PE 相关指标（收缩压和舒张压以及 24 小时蛋白尿水平）呈负相关。此外，功能获得实验证实 circ_0022707 可促进滋养细胞增殖和细胞周期进程，同时抑制细胞凋亡。在子痫前期样小鼠模型的体内实验中也表明，circ_0022707 的给药可减轻子痫前期样症状。从机制上讲，我们证实 circ_0022707 通过在滋养细胞中发挥 miR-3135b/GHR/PI3K/Akt 通路的作用。总的来说，本研究深入了解了 circ_0022707 在 PE 发展中的重要功能，增强了我们对该疾病机制的理解，并为 PE 提出了可行的治疗策略。
