Post-transcriptional regulation of MRE11 expression in muscle-invasive bladder tumours
| Autor: | Anne E. Kiltie, Mark Teo, Sarah J. Jevons, Bradly G. Wouters, Marianne Koritzinsky, Rebecca M. Martin, Martin Kerr, Selina Bhattarai |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Pathology
medicine.medical_specialty Transcription Genetic medicine.medical_treatment Cell Cycle Proteins Biology Cystectomy 03 medical and health sciences miR-153 0302 clinical medicine Cell Line Tumor microRNA medicine Humans Neoplasm Invasiveness RNA Messenger RNA Neoplasm Nuclear protein Post-transcriptional regulation 3' Untranslated Regions 030304 developmental biology 0303 health sciences Messenger RNA MRE11 Homologue Protein Bladder cancer Base Sequence Three prime untranslated region MRE11 Nuclear Proteins medicine.disease Immunohistochemistry 3. Good health Acid Anhydride Hydrolases DNA-Binding Proteins MicroRNAs enzymes and coenzymes (carbohydrates) DNA Repair Enzymes Oncology Urinary Bladder Neoplasms protein stability 030220 oncology & carcinogenesis Rad50 Protein Biosynthesis Cancer research bladder cancer Research Paper post-transcriptional regulation |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | Predictive assays are needed to help optimise treatment in muscle-invasive bladder cancer, where patients can be treated by either cystectomy or radical radiotherapy. Our finding that low tumour MRE11 expression is predictive of poor response to radiotherapy but not cystectomy was recently independently validated. Here we investigated further the mechanism underlying low MRE11 expression seen in poorly-responding patients. MRE11 RNA and protein levels were measured in 88 bladder tumour patient samples, by real-time PCR and immunohistochemistry respectively, and a panel of eight bladder cancer cell lines was screened for MRE11, RAD50 and NBS1 mRNA and protein expression. There was no correlation between bladder tumour MRE11 protein and RNA scores (Spearman's rho 0.064, p=0.65), suggesting MRE11 is controlled post-transcriptionally, a pattern confirmed in eight bladder cancer cell lines. In contrast, NBS1 and RAD50 mRNA and protein levels were correlated (p=0.01 and p=0.03, respectively), suggesting primary regulation at the level of transcription. MRE11 protein levels were correlated with NBS1 and RAD50 mRNA and protein levels, implicating MRN complex formation as an important determinant of MRE11 expression, driven by RAD50 and NBS1 expression. Our findings of the post-transcriptional nature of the control of MRE11 imply that any predictive assays used in patients need to be performed at the protein level rather than the mRNA level. |
| Databáze: | OpenAIRE |
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