Integrative analysis of dysregulated microRNAs and mRNAs in multiple recurrent synchronized renal tumors from patients with von Hippel-Lindau disease
| Autor: | Sophie Couvé, Nathalie Droin, Sophie Giraud, Virginie Verkarre, Mathieu Chiquet, Sophie Gad, Brigitte Bressac-De-Paillerets, Philippe Dessen, Betty Gardie, Viorel Vasiliu, Stéphane Richard, Bin Tean Teh, Arnaud Mejean, Sophie Ferlicot, Charles-Henry Gattolliat, Cedric Orear, Vincent Molinié, Guillaume Meurice |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine Cancer Research von Hippel-Lindau Disease Tumor suppressor gene Biology Kidney urologic and male genital diseases Neoplasms Multiple Primary Young Adult 03 medical and health sciences 0302 clinical medicine Germline mutation Cell Line Tumor microRNA medicine Humans miRNA and mRNA profiling RNA Messenger Von Hippel–Lindau disease Carcinoma Renal Cell Aged Oligonucleotide Array Sequence Analysis Aged 80 and over Regulation of gene expression Gene Expression Profiling Cancer Articles Middle Aged medicine.disease Molecular medicine Kidney Neoplasms clear-cell renal cell carcinoma Gene Expression Regulation Neoplastic Gene expression profiling MicroRNAs 030104 developmental biology Oncology Von Hippel-Lindau Tumor Suppressor Protein Case-Control Studies 030220 oncology & carcinogenesis Cancer research Female Neoplasm Recurrence Local integrative analyses |
| Zdroj: | International Journal of Oncology |
| ISSN: | 1791-2423 1019-6439 |
| Popis: | Von Hippel-Lindau (VHL) disease is a rare auto-somal dominant syndrome that is the main cause of inherited clear-cell renal cell carcinoma (ccRCC), which generally occurs in the form of multiple recurrent synchronized tumors. Affected patients are carriers of a germline mutation in the VHL tumor suppressor gene. Somatic mutations of this gene are also found in sporadic ccRCC and numerous pan-genomic studies have reported a dysregulation of microRNA (miRNA) expression in these sporadic tumors. In order to investigate the molecular mechanisms underlying the pathogenesis of VHL-associated ccRCC, particularly in the context of multiple tumors, the present study characterized the mRNA and miRNA transcriptome through an integrative analysis compared with sporadic renal tumors. In the present study, two series of ccRCC samples were used. The first set consisted of several samples from different tumors occurring in the same patient, for two independent patients affected with VHL disease. The second set consisted of 12 VHL-associated tumors and 22 sporadic ccRCC tumors compared with a pool of normal renal tissue. For each sample series, an expression analysis of miRNAs and mRNAs was conducted using microarrays. The results indicated that multiple tumors within the kidney of a patient with VHL disease featured a similar pattern of miRNA and gene expression. In addition, the expression levels of miRNA were able to distinguish VHL-associated tumors from sporadic ccRCC, and it was identified that 103 miRNAs and 2,474 genes were differentially expressed in the ccRCC series compared with in normal renal tissue. The majority of dysregulated genes were implicated in 'immunity' and 'metabolism' pathways. Taken together, these results allow a better understanding of the occurrence of ccRCC in patients with VHL disease, by providing insights into dysregulated miRNA and mRNA. In the set of patients with VHL disease, there were few differences in miRNA and mRNA expression, thus indicating a similar molecular evolution of these synchronous tumors and suggesting that the same molecular mechanisms underlie the pathogenesis of these hereditary tumors. |
| Databáze: | OpenAIRE |
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