Liu Lifang, Liu Hao, Jia Rui, Zhang Xiaoyan, Lu Xiaoxiao
School of Animal Husbandry and Biotechnology & School of Economics and Business, Mongolian University of Life Sciences, Ulaanbaatar, Mongolia.
Hebi Key Laboratory of Genetics and Birth Defects Prevention, Control Genetic and Prenatal Diagnosis Center of Hebi People's Hospital, Hebi, China.
Cytotechnology. 2025 Aug;77(4):124. doi: 10.1007/s10616-025-00782-y. Epub 2025 Jun 13.
Preeclampsia (PE) is one of the most common and serious documented gestational complications, and it is threatening the mother and the fetus, which is a notable burden on healthcare systems. Aldehyde dehydrogenase 1A1 (ALDH1A1), a cytosolic enzyme, shows vital physiological and pathophysiological functions in many areas. In the majority of cancer types, obesity-associated protein (FTO) is upregulated and exhibits an essential tumor-promoting role. We speculate that FTO and ALDH1A1 may play a significant role in the pathogenesis of PE by affecting the trophoblast cell biological behaviors. We analyzed differential expression genes (DEGs) in PE and non-PE groups in the GSE234726 dataset. The reverse-transcription quantitative polymerase chain reaction (qRT-PCR) and western blot assay were performed to test the mRNA and protein levels. The cell proliferation and apoptosis were examined using 5-Ethynyl-2'-deoxyuridine (EdU) and flow cytometry. The cell migration was investigated by wound healing assay and transwell assay. The ability of angiogenesis was tested by angiogenesis assay. The Spearman's rank correlation coefficient was used to analyze the correlation between ALDH1A1 expression and FTO expression. The m6A methylation site of ALDH1A1 mRNA was predicted using SRAMP website. The RNA immunoprecipitation (RIP) and m6A RNA immunoprecipitation (MeRIP) assay were performed to examine the binding relationship between ALDH1A1 and FTO. In PE, ALDH1A1 level is decreased. Silencing ALDH1A1 suppressed cell proliferation, migration, and angiogenesis and induced cell apoptosis. ALDH1A1 knockdown inhibited the expression of cyclin D1, anti-matrix metalloproteinase 9 (MMP9), and vascular endothelial growth factor (VEGF) and facilitated c-casp3 levels. The FTO expression was increased in PE placentas. Besides, the ALDH1A1 expression was negatively correlated with FTO levels, and FTO could target ALDH1A1. Mechanically, FTO repressed the biological behaviors of HTR-8/SVneo cells via ALDH1A1 down-regulation. FTO retards the HTR-8/SVneo cell biological function through knockdown of ALDH1A1. These results suggest that FTO and ALDH1A1 may play an important role in the pathogenesis of PE.
子痫前期（PE）是最常见且有文献记载的严重妊娠并发症之一，它威胁着母亲和胎儿，给医疗系统带来了显著负担。醛脱氢酶1A1（ALDH1A1）是一种胞质酶，在许多领域发挥着重要的生理和病理生理功能。在大多数癌症类型中，肥胖相关蛋白（FTO）上调并发挥重要的肿瘤促进作用。我们推测FTO和ALDH1A1可能通过影响滋养层细胞生物学行为在PE发病机制中发挥重要作用。我们分析了GSE234726数据集中PE组和非PE组的差异表达基因（DEG）。进行逆转录定量聚合酶链反应（qRT-PCR）和蛋白质免疫印迹分析以检测mRNA和蛋白质水平。使用5-乙炔基-2'-脱氧尿苷（EdU）和流式细胞术检测细胞增殖和凋亡。通过伤口愈合试验和Transwell试验研究细胞迁移。通过血管生成试验测试血管生成能力。使用Spearman等级相关系数分析ALDH1A1表达与FTO表达之间的相关性。使用SRAMP网站预测ALDH1A1 mRNA的m6A甲基化位点。进行RNA免疫沉淀（RIP）和m6A RNA免疫沉淀（MeRIP）试验以检测ALDH1A1与FTO之间的结合关系。在PE中，ALDH1A1水平降低。沉默ALDH1A1可抑制细胞增殖、迁移和血管生成并诱导细胞凋亡。敲低ALDH1A1可抑制细胞周期蛋白D1、抗基质金属蛋白酶9（MMP9）和血管内皮生长因子（VEGF）的表达并促进c-casp3水平。PE胎盘组织中FTO表达增加。此外，ALDH1A1表达与FTO水平呈负相关，且FTO可靶向ALDH1A1。从机制上讲，FTO通过下调ALDH1A1抑制HTR-8/SVneo细胞的生物学行为。FTO通过敲低ALDH1A1延缓HTR-8/SVneo细胞生物学功能。这些结果表明FTO和ALDH1A1可能在PE发病机制中起重要作用。
