Lifang Liu, Hao Liu, Rui Jia, Xiaoyan Zhang, Xiaoxiao Lu
{"title":"FTO curbs trophoblast cell biological behaviors through repressing ALDH1A1 expression.","authors":"Lifang Liu, Hao Liu, Rui Jia, Xiaoyan Zhang, Xiaoxiao Lu","doi":"10.1007/s10616-025-00782-y","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"77 4","pages":"124"},"PeriodicalIF":2.0000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12165930/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cytotechnology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s10616-025-00782-y","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/6/13 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
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.
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.