超级增强子介导GSE1的转录并通过Wnt/β-catenin信号通路促进乳腺癌细胞增殖的机制

doi:10.3969/j.issn.1006-5725.2025.18.003

Abstract

Abstract:

Objective To investigate the molecular mechanism by which super enhancers （SEs） regulate the expression of the genetic suppressor element 1 （GSE1） and influence the proliferation of breast cancer cell line MCF-7. Methods The oncogene GSE1， driven by SEs， was identified through analysis of the ChIP-seq dataset of MCF-7 cells obtained from the GEO database. The protein expression level of GSE1 was assessed via Western blot following treatment with the bromodomain-containing protein 4 （BRD4） inhibitor JQ1. The expression of GSE1 across various cancers and different breast cancer subtypes was analyzed using the Human Protein Atlas （HPA） and The Cancer Genome Atlas （TCGA） databases， respectively. Overall survival （OS） of breast cancer patients was compared between the GSE1 high-expression and low-expression groups using the GEPIA database. Immunohistochemistry （IHC） was performed to evaluate GSE1 expression in breast cancer tissue samples. The mRNA expression levels of GSE1 in different breast cancer cell lines were validated by RT-qPCR. A GSE1 interference vector was constructed and transfected into MCF-7 cells， and the knockdown efficiency was assessed using Western blot. Cell proliferation and migration were evaluated using CCK-8 assay， colony formation assay， wound healing assay， and Transwell migration assay. Potential GSE1-interacting proteins were predicted using the STRING database. Finally， Western blot analysis was conducted to assess changes in epithelial-mesenchymal transition （EMT）-related proteins and key components of the Wnt/β-catenin signaling pathway. Results The integrative genomics viewer （IGV） was used to visualize ChIP-seq data from MCF-7 cells， and the rank ordering of super enhancers （ROSE） algorithm was applied to predict the SE region of GSE1 in the MCF-7 genome. GSE1 and BRD4 expression levels were significantly reduced following JQ1 treatment （P < 0.05）. High expression levels of GSE1 in breast cancer were confirmed through analyses using the HPA， TCGA， and GEPIA databases， as well as IHC， and these findings were associated with poor prognostic outcomes in breast cancer patients （P < 0.05）. RT-qPCR results further demonstrated that GSE1 is significantly upregulated in breast cancer cells （P < 0.05）. Analysis of the STRING database revealed a strong correlation between GSE1 and Snail （Snai1）. Transfection of a GSE1-specific interference vector significantly inhibited the proliferation and migration of MCF-7 cells compared to the control group， upregulated E-cadherin and Occludin expression， and downregulated N-cadherin and Snail expression （P < 0.05）. Additionally， knockdown of GSE1 resulted in decreased expression of Wnt/β-catenin signaling pathway-related proteins， including β-catenin， Wnt-5a， and Cyclin-D1， along with increased Axin1 expression （P < 0.05）. Conclusion SE driven GSE1 promotes the proliferation， migration and EMT of MCF-7 cells via the Wnt/β-catenin signaling pathway.

Key words: super-enhancer, GSE1, epithelial-mesenchymal transition, proliferation, migration, Wnt/β-catenin signaling pathway

CLC Number:

R737.9

Peijing DU,Enxi HU,Xiang TAO,Jia CAO,Libin WANG. Super⁃enhancer⁃mediated GSE1 activation drives breast cancer proliferation through Wnt/β⁃catenin signaling[J]. The Journal of Practical Medicine, 2025, 41(18): 2796-2805.

Figures/Tables 6

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Super⁃enhancer⁃mediated GSE1 activation drives breast cancer proliferation through Wnt/β⁃catenin signaling

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