SNAI1 promotes epithelial-mesenchymal transition and maintains cancer stem cell-like properties in thymic epithelial tumors through the PIK3R2/p-EphA2 Axis

作者：E Haoran, Lei Zhang, Zhenhua Yang, Long Xu, Tao Wang, Junhong Guo, Lang Xia, Juemin Yu, Heyong Wang, Yunlang She, Junqi Wu, Yue Zhao, Chang Chen, Deping Zhao · 发表于：Journal of Experimental & Clinical Cancer Research · 年份：2024 · DOI：10.1186/s13046-024-03243-0 · 被引用次数：10 · 研究领域：Myasthenia Gravis and Thymoma、Glioma Diagnosis and Treatment、Single-cell and spatial transcriptomics

BACKGROUND: Thymic epithelial tumors (TETs) are infrequent malignancies that arise from the anterior mediastinum. Therapeutic options for TETs, especially thymic carcinoma (TC), remain relatively constrained. This study aims to investigate the oncogenic hub gene and its underlying mechanisms in TETs, as well as to identify potential therapeutic targets. METHODS: Weighted gene co-expression network analysis (WGCNA) and differential gene expression (DEG) analysis were utilized to identify significant oncogenes using The Cancer Genome Atlas (TCGA) database. LASSO logistic regression analysis was performed to assess the association between hub genes and clinical parameters. The influence of the hub gene on promoting epithelial-mesenchymal transition (EMT), tumor progression, and regulating cancer stem cell-like properties was assessed both in vitro and in vivo. Single-cell RNA sequencing (scRNA-seq) was utilized to analyze the alterations in the tumor and its microenvironment following the administration of the hub gene's inhibitor. Multiplex immunohistochemistry (mIHC) was employed to validate the results. The potential mechanism was further elucidated through the utilization of Cleavage Under Targets and Tagmentation (CUT&Tag), RNA-sequencing, chromatin immunoprecipitation (ChIP), CUT&RUN, luciferase reporter assay, co-immunoprecipitation (Co-IP), mass spectrometry (MS) and phosphoproteomic assays. RESULTS: SNAI1 was identified as a hub transcription factor for TETs, and its po...