Xiyun Quan , Huimei Yi , Meiyuan Huang, Dongliang Chen
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引用次数: 0
Abstract
Background
Angiogenesis assumes an essential role in tumor development and is a fundamental condition for tumor growth. Yin Yang 1 (YY1) is highly expressed in various types of cancers and is a key player in tumor angiogenesis, but its role in ovarian cancer (OC) has not been fully elucidated. Therefore, this study will delve into the mechanism of YY1 in OC angiogenesis.
Methods
Based on single-cell transcriptomics data of OC tumor samples and adjacent samples downloaded from the GEO database, differentially expressed genes (DEGs) and related signaling pathways were screened and validated in OC cells. Furthermore, co-culture technology was applied to assess the impact of YY1 expression in OC cells on angiogenesis ability. The molecular mechanism of YY1 regulation of OC angiogenesis was explored through bioinformatics analysis combined with co-immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter gene assays. Rescue experiments were designed, with results validated in qRT-PCR, angiogenesis assays, and Western blotting.
Results
Based on re-analysis of single-cell transcriptomics data from OC tumor samples and adjacent samples, we found that YY1 expression was significantly upregulated in OC cells, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis results showed that DEGs in YY1-positive tumor cells were significantly enriched in the HIF-1 signaling pathway. Moreover, in vitro experiments demonstrated that YY1 was highly expressed in OC to boost OC angiogenesis. Specifically, YY1 can stabilize hypoxia-inducible factor 1α (HIF1A) expression by competitively binding to WD repeat domain-containing 7 (FBXW7), thereby facilitating the transcriptional activation of angiogenesis genes. Finally, we demonstrated through rescue experiments that targeting the YY1/HIF1A axis can repress OC angiogenesis.
Conclusion
Through single-cell transcriptomics analysis combined with cell experiments, we proved the specific mechanism by which YY1 affects the angiogenesis ability of OC. YY1 affects the expression of angiogenesis genes by modulating the FBXW7/HIF1A axis.
期刊介绍:
Mutation Research (MR) provides a platform for publishing all aspects of DNA mutations and epimutations, from basic evolutionary aspects to translational applications in genetic and epigenetic diagnostics and therapy. Mutations are defined as all possible alterations in DNA sequence and sequence organization, from point mutations to genome structural variation, chromosomal aberrations and aneuploidy. Epimutations are defined as alterations in the epigenome, i.e., changes in DNA methylation, histone modification and small regulatory RNAs.
MR publishes articles in the following areas:
Of special interest are basic mechanisms through which DNA damage and mutations impact development and differentiation, stem cell biology and cell fate in general, including various forms of cell death and cellular senescence.
The study of genome instability in human molecular epidemiology and in relation to complex phenotypes, such as human disease, is considered a growing area of importance.
Mechanisms of (epi)mutation induction, for example, during DNA repair, replication or recombination; novel methods of (epi)mutation detection, with a focus on ultra-high-throughput sequencing.
Landscape of somatic mutations and epimutations in cancer and aging.
Role of de novo mutations in human disease and aging; mutations in population genomics.
Interactions between mutations and epimutations.
The role of epimutations in chromatin structure and function.
Mitochondrial DNA mutations and their consequences in terms of human disease and aging.
Novel ways to generate mutations and epimutations in cell lines and animal models.