FTO curbs trophoblast cell biological behaviors through repressing ALDH1A1 expression.

IF 2 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Cytotechnology Pub Date : 2025-08-01 Epub Date: 2025-06-13 DOI:10.1007/s10616-025-00782-y
Lifang Liu, Hao Liu, Rui Jia, Xiaoyan Zhang, Xiaoxiao Lu
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引用次数: 0

Abstract

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.

FTO通过抑制ALDH1A1表达来抑制滋养细胞的生物学行为。
先兆子痫(PE)是最常见和最严重的妊娠并发症之一,它威胁着母亲和胎儿,是医疗保健系统的一个显着负担。醛脱氢酶1A1 (ALDH1A1)是一种细胞质酶,在许多领域具有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,并表现出重要的肿瘤促进作用。我们推测FTO和ALDH1A1可能通过影响滋养细胞的生物学行为在PE的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(DEGs)。采用反转录定量聚合酶链反应(qRT-PCR)和western blot检测mRNA和蛋白水平。用5-乙基-2′-脱氧尿苷(EdU)和流式细胞术检测细胞增殖和凋亡情况。采用伤口愈合实验和transwell实验研究细胞迁移。采用血管生成法检测其血管生成能力。采用Spearman秩相关系数分析ALDH1A1表达与FTO表达的相关性。使用SRAMP网站预测ALDH1A1 mRNA的m6A甲基化位点。采用RNA免疫沉淀法(RIP)和m6A RNA免疫沉淀法(MeRIP)检测ALDH1A1与FTO的结合关系。在PE中,ALDH1A1水平降低。沉默ALDH1A1抑制细胞增殖、迁移和血管生成,诱导细胞凋亡。ALDH1A1敲低可抑制细胞周期蛋白D1、抗基质金属蛋白酶9 (MMP9)、血管内皮生长因子(VEGF)的表达,促进c-casp3水平。FTO在PE胎盘中表达增加。此外,ALDH1A1表达与FTO水平呈负相关,FTO可以靶向ALDH1A1。机械上,FTO通过下调ALDH1A1抑制HTR-8/SVneo细胞的生物学行为。FTO通过下调ALDH1A1来延缓HTR-8/SVneo细胞的生物学功能。这些结果提示FTO和ALDH1A1可能在PE的发病机制中起重要作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cytotechnology
Cytotechnology 生物-生物工程与应用微生物
CiteScore
4.10
自引率
0.00%
发文量
49
审稿时长
6-12 weeks
期刊介绍: The scope of the Journal includes: 1. The derivation, genetic modification and characterization of cell lines, genetic and phenotypic regulation, control of cellular metabolism, cell physiology and biochemistry related to cell function, performance and expression of cell products. 2. Cell culture techniques, substrates, environmental requirements and optimization, cloning, hybridization and molecular biology, including genomic and proteomic tools. 3. Cell culture systems, processes, reactors, scale-up, and industrial production. Descriptions of the design or construction of equipment, media or quality control procedures, that are ancillary to cellular research. 4. The application of animal/human cells in research in the field of stem cell research including maintenance of stemness, differentiation, genetics, and senescence, cancer research, research in immunology, as well as applications in tissue engineering and gene therapy. 5. The use of cell cultures as a substrate for bioassays, biomedical applications and in particular as a replacement for animal models.
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