Circular RNA circ_0022707 impedes the progression of preeclampsia via the miR-3135b/GHR/PI3K/Akt axis

Abstract

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.