Expression analysis of TOP2A, MSH2 and MLH1 genes in MCF7 cells at different levels of etoposide resistance

Kaplan, Esra; Gündüz, Ufuk

doi:10.1016/j.biopha.2011.09.002

Cited by 23 publications

(12 citation statements)

References 24 publications

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“…TOP2A (topoisomerase (DNA) II alpha), a nuclear enzyme which is involved in cell division and cell cycle, was identified as one of the hub genes exhibiting the highest degree of connectivity in current study. Kaplan et al [ 13 ] demonstrated that TOP2A represented a direct molecular target of anthracyclin-based chemotherapy and topoisomerase inhibitor, such as etoposide. It has also reported that TOP2A was the well-known good prognostic marker in breast cancers, which was associated with a favorable response to anthracyclin-based therapy [ 14 – 16 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of genes and pathways in nasopharyngeal carcinoma by bioinformatics analysis

et al. 2017

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Nasopharyngeal carcinoma is a metastatic malignant tumor originating from nasopharyngeal epithelium. Lacking or nonspecific symptoms of patients with early stage nasopharyngeal carcinoma have significantly reduced the accuracy of diagnosing and predicting nasopharyngeal carcinoma development. This study aimed to identify gene signatures of nasopharyngeal carcinoma and uncover potential mechanisms. Two gene expression profiles (GSE12452 and GSE13597) containing 56 nasopharyngeal carcinoma samples and 13 normal control samples were analyzed to identify the differentially expressed genes. In total, 179 up-regulated genes and 238 down-regulated genes were identified. Functional and pathway enrichment analysis showed that up-regulated genes were significantly involved in cell cycle, oocyte meiosis, DNA replication and p53 signaling pathway, while down-regulated genes were enriched in Huntington's disease,metabolic pathways. Subsequently, the top 10 hub genes, TOP2A (topoisomerase (DNA) II alpha), CDK1 (cyclin-dependent kinase 1), CCNB1 (cyclin B1), PCNA (proliferating cell nuclear antigen), MAD2L1 (mitotic arrest deficient 2 like 1), BUB1 (budding uninhibited by benzimidazoles 1 homolog), CCNB2 (cyclin B2), AURKA (aurora kinase A), CCNA2 (cyclin A2), CDC6 (cell division cycle 6 homolog), were identified from protein-protein interaction network. Furthermore, Module analysis revealed that the ten hub genes except TOP2A were belonged to module 1, indicating the upregulation of these hub genes associated molecular pathways in nasopharyngeal carcinoma might activate nasopharyngeal carcinoma pathogenesis. In conclusion, this study indicated that the identified differentially expressed genes and hub genes enrich our understanding of the molecular mechanisms of nasopharyngeal carcinoma, which could eventually translate into additional biomarkers to facilitate the early diagnosis and therapeutic approaches.

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Section: Discussionmentioning

confidence: 99%

Identification of genes and pathways in nasopharyngeal carcinoma by bioinformatics analysis

et al. 2017

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“…The effect could be due to several effects including heterogeneity in the drug availability at the metastatic sites, heterogeneity as a consequence of mechanisms spontaneously conferring resistance to etoposide treatment, heterogeneity due to clonal selection under genotoxic stress, or the more recently discovered effect of immune microenvironment differences on chemotherapy response (43). The genetics-based hypotheses are strengthened by 2 recent studies reporting on differences in gene and micro RNA expression in human breast cancer cell lines that were either sensitive or resistant to etoposide (44,45). Clearly, more in-depth research is necessary to unravel the precise cause for this heterogenic behavior under etoposide treatment.…”

Section: Discussionmentioning

confidence: 99%

A Whole-Body Dual-Modality Radionuclide Optical Strategy for Preclinical Imaging of Metastasis and Heterogeneous Treatment Response in Different Microenvironments

et al. 2014

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Imaging spontaneous cancer cell metastasis or heterogeneous tumor responses to drug treatment in vivo is difficult to achieve. The goal was to develop a new highly sensitive and reliable preclinical longitudinal in vivo imaging model for this purpose, thereby facilitating discovery and validation of anticancer therapies or molecular imaging agents. Methods: The strategy is based on breast cancer cells stably expressing the human sodium iodide symporter (NIS) fused to a red fluorescent protein, thereby permitting radionuclide and fluorescence imaging. Using whole-body nano-SPECT/CT with 99m TcO 4 − , we followed primary tumor growth and spontaneous metastasis in the presence or absence of etoposide treatment. NIS imaging was used to classify organs as small as individual lymph nodes (LNs) to be positive or negative for metastasis, and results were confirmed by confocal fluorescence microscopy. Etoposide treatment efficacy was proven by ex vivo anticaspase 3 staining and fluorescence microscopy. Results: In this preclinical model, we found that the NIS imaging strategy outperformed stateof-the-art 18 F-FDG imaging in its ability to detect small tumors (18.5-fold-better tumor-to-blood ratio) and metastases (LN, 3.6-fold) because of improved contrast in organs close to metastatic sites (12-and 8.5-fold-lower standardized uptake value in the heart and kidney, respectively). We applied the model to assess the treatment response to the neoadjuvant etoposide and found a consistent and reliable improvement in spontaneous metastasis detection. Importantly, we also found that tumor cells in different microenvironments responded in a heterogeneous manner to etoposide treatment, which could be determined only by the NIS-based strategy and not by 18 F-FDG imaging. Conclusion: We developed a new strategy for preclinical longitudinal in vivo cancer cell tracking with greater sensitivity and reliability than 18 F-FDG PET and applied it to track spontaneous and distant metastasis in the presence or absence of genotoxic stress therapy. Importantly, the model provides sufficient sensitivity and dynamic range to permit the reliable assessment of heterogeneous treatment responses in various microenvironments.

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“…TOP2A, which encodes a DNA topoisomerase, is associated with various processes, including chromosome condensation (32). Mutations in TOP2A are associated with the development of drug resistance, including etoposide and doxorubicin (33)(34)(35). Exposure to atmospheric oxygen promotes TOP2A expression in mouse MSCs, leading to oxidative stress, reduced cell viability and the inhibition of cell proliferation (36).…”

Section: Discussionmentioning

confidence: 99%

Identification of core genes and prediction of miRNAs associated with osteoporosis using a bioinformatics approach

Chai

Tan

et al. 2018

Oncol Lett

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Osteoporosis (OP) is an age-related disease, and osteoporotic fracture is one of the major causes of disability and mortality in elderly patients (>70 years old). As the pathogenesis and molecular mechanism of OP remain unclear, the identification of disease biomarkers is important for guiding research and providing therapeutic targets. In the present study, core genes and microRNAs (miRNAs) associated with OP were identified. Differentially expressed genes (DEGs) between human mesenchymal stem cell specimens from normal osseous tissues and OP tissues were detected using the GEO2R tool of the Gene Expression Omnibus database and Morpheus. Network topological parameters were determined using NetworkAnalyzer. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery, and ClueGO. Cytoscape with the Search Tool for the Retrieval of Interacting Genes and Molecular Complex Detection plug-in was used to visualize protein-protein interactions (PPIs). Additionally, miRNA-gene regulatory modules were predicted using CyTargetLinker in order to guide future research. In total, 915 DEGs were identified, including 774 upregulated and 141 downregulated genes. Enriched GO terms and pathways were determined, including 'nervous system development', 'regulation of molecular function', 'glutamatergic synapse pathway' and 'pathways in cancer'. The node degrees of DEGs followed power-law distributions. A PPI network with 541 nodes and 1,431 edges was obtained. Overall, 3 important modules were identified from the PPI network. The following 10 genes were identified as core genes based on high degrees of connectivity: Albumin, PH domain leucine-rich repeat-containing protein phosphatase 2 (PHLPP2), DNA topoisomerase 2-α, kininogen 1 (KNG1), interleukin 2 (IL2), leucine-rich repeats and guanylate kinase domain containing, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit γ (PIK3CG), leptin, transferrin and RNA polymerase II subunit A (POLR2A). Additionally, 15 miRNA-target interactions were obtained using CyTargetLinker. Overall, 7 miRNAs co-regulated IL2, 3 regulated PHLPP2, 3 regulated KNG1, 1 regulated PIK3CG and 1 modulated POLR2A. These results indicate potential biomarkers in the pathogenesis of OP and therapeutic targets.

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Expression analysis of TOP2A, MSH2 and MLH1 genes in MCF7 cells at different levels of etoposide resistance

Cited by 23 publications

References 24 publications

Identification of genes and pathways in nasopharyngeal carcinoma by bioinformatics analysis

Identification of genes and pathways in nasopharyngeal carcinoma by bioinformatics analysis

A Whole-Body Dual-Modality Radionuclide Optical Strategy for Preclinical Imaging of Metastasis and Heterogeneous Treatment Response in Different Microenvironments

Identification of core genes and prediction of miRNAs associated with osteoporosis using a bioinformatics approach

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