Quantitative Proteomics Analysis Reveals Nuclear Perturbation in Human Glioma U87 Cells treated with Temozolomide
| Autor: | Songtao Qi, Haimin Song, Manlan Guo, Xiran Wang, Yawei Liu, Guozhong Yi, Xuegang Sun, Yaomin Li, Guanglong Huang, Kaishu Li, Jinglin Guo, Ke Li, Zhifeng Liu, Runwei Yang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Proteomics Spectrometry Mass Electrospray Ionization DNA Repair Proteome DNA damage Clinical Biochemistry Quantitative proteomics Biology Biochemistry 03 medical and health sciences 0302 clinical medicine Glioma Cell Line Tumor Protein Interaction Mapping medicine Temozolomide Humans Nuclear protein neoplasms Cell Nucleus Brain Neoplasms Computational Biology Cell Biology General Medicine medicine.disease 030104 developmental biology MSH2 030220 oncology & carcinogenesis Cancer research Glioblastoma medicine.drug DNA Damage Protein Binding |
| Zdroj: | Cell biochemistry and functionREFERENCES. 38(2) |
| ISSN: | 1099-0844 |
| Popis: | Glioblastoma (GBM) is the most malignant and aggressive glioma, which has a very poor prognosis. Temozolomide (TMZ) is still a first-line treatment, but resistance is inevitable even in MGMT-deficient glioblastoma cells. The aims of this study were to comprehend the effect of TMZ on nucleus and the underlying mechanism of acquired TMZ resistance in MGMT-deficient GBM. We show the changes of nuclear proteome in the MGMT-deficient GBM U87 cells treated with TMZ for 1 week. Label-free-based quantitative proteomics were used to investigate nuclear protein abundance change. Subsequently, gene ontology function annotation, KEGG pathway analysis, protein-protein interaction (PPI) network construction analysis of DAPs, and immunofluorescence were applied to validate the quality of proteomics. In total, 457 (455 gene products) significant DAPs were identified, of which 327 were up-regulated and 128 were down-regulated. Bioinformatics analysis uncovered RAD50, MRE11, UBR5, MSH2, MSH6, DDB1, DDB2, RPA1, RBX1, CUL4A, and CUL4B mainly enriched in DNA damage repair related pathway and constituted a protein-protein interaction network. Ribosomal proteins were down-regulated. Cells were in a stress-responsive state, while the entire metabolic level was lowered. SIGNIFICANCE OF THE STUDY: In U87 cell treated with TMZ for 1 week, which resulted in DNA damage, we found various proteins dysregulated in the nucleus. Some proteins related to the DNA damage repair pathway were up-regulated, and there was a strong interaction. We believe this is the potential clues of chemotherapy resistance in tumour cells. These proteins can be used as indicators of tumour resistance screening in the future. |
| Databáze: | OpenAIRE |
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