长非编码RNA(lncRNA)表达异常已被证明参与子痫前期(PE)的病理过程,然而,只有一小部分lncRNAs被表征为涉及PE的功能和分子机制。本研究旨在探讨lncRNAAC092100.1(AC092100.1)在PE血管生成中的调控机制。在我们的研究中,进行生物信息学分析以筛选正常受试者和PE患者之间差异表达的lncRNAs。使用qRT-PCR验证有或没有PE的患者的胎盘组织中AC092100.1的水平。AC092100.1过表达对细胞增殖的影响,迁移,并研究了人脐静脉内皮细胞(HUVECs)的管形成。预测并验证了AC092100.1和含有YT521-B同源结构域的2(YTHDC2)的结合。确定AC092100.1/YTHDC2对HUVECs中血管内皮生长因子-A(VEGFA)表达的影响。最后,进行PE小鼠模型。胎鼠生长,间充质形态标记的丰度,包括缺氧诱导因子1-α(HIF-1α),可溶性fms样酪氨酸激酶-1(sFlt-1),可溶性内皮糖蛋白(sEng),子弹,还有Vimentin,和内皮标记物,包括胎盘生长因子(PLGF),CD31和血管内皮(VE)-钙黏着蛋白,在胎盘组织进行了评估。这里,我们发现AC092100.1在PE患者的胎盘组织中异常下调.我们确定AC092100.1过表达促进HUVEC增殖,迁移,和体外试管形成。机械上,AC092100.1通过与HUVEC中的YTHDC2结合诱导YTHDC2和VEGFA的积累。YTHDC2或VEGFA的抑制逆转了AC092100.1促进的管形成。AC092100.1过表达有助于减轻胎儿生长障碍,sEng水平降低,HIF-1α,sFlt-1,子弹,还有Vimentin,和增加的VEGFA水平,PLGF,PE小鼠中的CD31和VE-钙黏着蛋白。我们的发现提供了支持AC092100.1/YTHDC2/VEGFA轴在调节血管生成中的作用的证据。这证明了PE靶向血管生成的治疗途径。
Aberrant long non-coding RNA (lncRNA) expression has been shown to be involved in the pathological process of pre-eclampsia (PE), yet only a small portion of lncRNAs has been characterized concerning the function and molecular mechanisms involved in PE. This study aimed to investigate the regulatory mechanism of the lncRNA AC092100.1 (AC092100.1) in angiogenesis in PE. In our study, bioinformatics analysis was performed to screen for differentially expressed lncRNAs between normal subjects and PE patients. The levels of AC092100.1 in placental tissues of patients with or without PE were validated using qRT-PCR. The effect of AC092100.1 overexpression on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) was investigated. The binding of AC092100.1 and YT521-B homology domain-containing 2 (YTHDC2) was predicted and verified. The effect of AC092100.1/YTHDC2 on the expression of vascular endothelial growth factor-A (
VEGFA) in HUVECs was determined. Finally, a PE mice model was conducted. Fetal mouse growth, the abundance of mesenchymal morphology markers, including hypoxia-inducible factor 1-alpha (HIF-1α), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng), Slug, and Vimentin, and endothelial markers, including placental growth factor (PLGF), CD31, and vascular endothelial (VE)-cadherin, in placental tissues were assessed. Here, we found that AC092100.1 was abnormally downregulated in placental tissues from PE patients. We established that AC092100.1 overexpression promoted HUVEC proliferation, migration, and tube formation in vitro. Mechanistically, AC092100.1 induced the accumulation of YTHDC2 and
VEGFA through binding to YTHDC2 in HUVECs. Inhibition of YTHDC2 or
VEGFA reversed AC092100.1-promoted tube formation. AC092100.1 overexpression contributed to alleviating fetal growth disorder, decreased levels of sEng, HIF-1α, sFlt-1, Slug, and Vimentin, and increased levels of
VEGFA, PLGF, CD31, and VE-cadherin in PE mice. Our findings provided evidence supporting the role of the AC092100.1/YTHDC2/
VEGFA axis in regulating angiogenesis, which demonstrated a therapeutic pathway for PE targeting angiogenesis.