Deciphering the molecular mechanism of YY1/HIF1A modulating ovarian cancer angiogenesis based on single-cell transcriptomics technology

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.

Angiogenesis; HIF1A; Ovarian cancer; Single-cell transcriptomics; Yin Yang 1.