环状 RNA circ_0022707 通过 miR-3135b/GHR/PI3K/Akt 轴阻碍先兆子痫的发展。

IF 3.9 4区 生物学 Q1 GENETICS & HEREDITY
Huijing Shao, Rui Guan, Zixi Chen, Ruijiao Kong, Caihong Zhang, Hang Gu
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引用次数: 0

摘要

子痫前期(PE)是一种严重的妊娠并发症,与母体和胎儿的健康息息相关,但其根本原因和发病机理却仍然难以捉摸。环状 RNA(circRNA)是一种非编码 RNA,与子痫前期的进展有关联;但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,我们利用 GEO 数据库中的数据集构建了一个 ceRNA 网络,并确定 circ_0022707 为我们的研究目标。然后,通过 qRT-PCR 分析,我们验证了与正常孕妇相比,circ_0022707 在先兆子痫胎盘中的下调。原位杂交试验显示,circ_0022707存在于胎盘绒毛滋养层细胞中。此外,皮尔逊相关分析显示,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,功能增益实验证实,circ_0022707 可促进滋养层细胞增殖和细胞周期进展,同时抑制细胞凋亡。使用子痫前期样小鼠模型进行的体内实验也证明,服用 circ_0022707 可减轻子痫前期样症状。从机理上讲,我们证实 circ_0022707 是通过滋养层细胞中的 miR-3135b/GHR/PI3K/Akt 通路发挥作用的。总之,我们的研究深入揭示了 circ_002707 在 PE 发病过程中的重要功能,加深了我们对 PE 发病机制的理解,并提出了一种可行的 PE 治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Circular RNA circ_0022707 impedes the progression of preeclampsia via the miR-3135b/GHR/PI3K/Akt axis

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.

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来源期刊
CiteScore
3.50
自引率
3.40%
发文量
92
审稿时长
2 months
期刊介绍: Functional & Integrative Genomics is devoted to large-scale studies of genomes and their functions, including systems analyses of biological processes. The journal will provide the research community an integrated platform where researchers can share, review and discuss their findings on important biological questions that will ultimately enable us to answer the fundamental question: How do genomes work?
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