Identification and characterization of critical genes associated with tamoxifen resistance in breast cancer
| Autor: | Ge Qin, Fei Xu, Kuikui Jiang, Shusen Wang, Qianyi Lu, Ruoxi Hong, Wen Xia, Qinglian Zhai, Kai Zhang, Qiufan Zheng, Kaping Lee |
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| Rok vydání: | 2020 |
| Předmět: |
Small interfering RNA
Drugs and Devices Bioinformatics Crucial genes Computational biology Biology General Biochemistry Genetics and Molecular Biology Telomere organization 03 medical and health sciences 0302 clinical medicine Breast cancer Bioinformatics analysis Gene expression medicine KEGG skin and connective tissue diseases Gene Molecular Biology 030304 developmental biology 0303 health sciences Gene knockdown General Neuroscience General Medicine medicine.disease Tamoxifen Oncology 030220 oncology & carcinogenesis Drug resistance General Agricultural and Biological Sciences Medical Genetics medicine.drug |
| Zdroj: | PeerJ |
| ISSN: | 2167-8359 |
| Popis: | Background Tamoxifen resistance in breast cancer is an unsolved problem in clinical practice. The aim of this study was to determine the potential mechanisms of tamoxifen resistance through bioinformatics analysis. Methods Gene expression profiles of tamoxifen-resistant MCF-7/TR and MCF-7 cells were acquired from the Gene Expression Omnibus dataset GSE26459, and differentially expressed genes (DEGs) were detected with R software. We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses using Database for Annotation, Visualization and Integrated Discovery. A protein–protein interaction (PPI) network was generated, and we analyzed hub genes in the network with the Search Tool for the Retrieval of Interacting Genes database. Finally, we used siRNAs to silence the target genes and conducted the MTS assay. Results We identified 865 DEGs, 399 of which were upregulated. GO analysis indicated that most genes are related to telomere organization, extracellular exosomes, and binding-related items for protein heterodimerization. PPI network construction revealed that the top 10 hub genes—ACLY, HSPD1, PFAS, GART, TXN, HSPH1, HSPE1, IRAS, TRAP1, and ATIC—might be associated with tamoxifen resistance. Consistently, RT-qPCR analysis indicated that the expression of these 10 genes was increased in MCF-7/TR cells comparing with MCF-7 cells. Four hub genes (TXN, HSPD1, HSPH1 and ATIC) were related to overall survival in patients who accepted tamoxifen. In addition, knockdown of HSPH1 by siRNA may lead to reduced growth of MCF-7/TR cell with a trend close to significance (P = 0.07), indicating that upregulation of HSPH1 may play a role in tamoxifen resistance. Conclusion This study revealed a number of critical hub genes that might serve as therapeutic targets in breast cancer resistant to tamoxifen and provided potential directions for uncovering the mechanisms of tamoxifen resistance. |
| Databáze: | OpenAIRE |
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