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Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:

2024 20

Page:

3857-3863

Research Field:

Publishing date:

Info

Title:

Research of tamoxifen resistance related glycolysis genes in breast cancer based on GEO database and its mechanism

Author(s):

XIA Jialin¹; ZHAO Weiwei²; LI Jing¹; 2

1.School of Laboratory Medicine and Biotechnology,Southern Medical University,Guangdong Guangzhou 510515,China;2.Affiliated Sixth People's Hospital South Campus,Shanghai Jiao Tong University,Shanghai 201400,China.

Keywords:

breast cancer; tamoxifen resistance; glycolysis; PYGL

PACS:

R737.9

DOI:

10.3969/j.issn.1672-4992.2024.20.007

Abstract:

Objective:To identify glycolysis-related gene markers associated with tamoxifen resistance(TamR) in breast cancer(BC) and provide a theoretical basis for understanding the mechanism of drug resistance.Methods:We downloaded the dataset GSE67916 from the Gene Expression Omnibus(GEO) database and performed differential analysis.The differentially expressed genes(DEGs) were intersected with the glycolysis-related gene set,and Gene Set Enrichment Analysis(GSEA) was conducted to identify glycolysis-related genes associated with tamoxifen resistance.The identified resistant genes were further validated in two external independent dataset,GSE125738 and GSE9893.In addition,qRT-PCR and Western blot techniques were used to validate the mRNA and protein expression of the resistant genes in the constructed tamoxifen-resistant cell line.CCK-8 experiments were conducted to further validate the role of resistant genes.Results:A total of 730 DEGs were obtained from the differential analysis,and 19 DEGs were identified by intersecting with the glycolysis-related gene set.GSEA enrichment analysis of these 19 DEGs revealed that PYGL were associated with tamoxifen resistance signaling pathway and endocrine therapy resistance signaling pathway.The upregulation of PYGL in the tamoxifen-resistant group was validated in the datasets GSE125738 and GSE9893.In the tamoxifen-resistant breast cancer cell line,both the mRNA and protein levels of PYGL were upregulated.Furthermore,CCK-8 experiments demonstrated that downregulation of PYGL expression enhanced the reactivity of MCF7-TamR to tamoxifen.Conclusion:Glycolytic gene PYGL is a potential tamoxifen resistance gene in breast cancer,which may provide new understanding and targeting strategies for breast cancer therapy.

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