Identification of protein-coding and intronic noncoding RNAs down-regulated in clear cell renal carcinoma

Autor(es)

Brito, Glauber Costa ^[1] ; Fachel, Angela A. ^[1] ; Vettore, Andre Luiz ^[2] ; Vignal, Giselle M. ^[3] ; Gimba, Etel R. P. ^[3] ; Campos, Franz S. ^[3] ; Barcinski, Marcello A. ^[3] ; Verjovski-Almeida, Sergio ^[1] ; Reis, Eduardo M. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05508 Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Sao Paulo - Brazil

^[3] Hosp Canc, Inst Nacl Canc MS, Rio De Janeiro - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecular Carcinogenesis; v. 47, n. 10, p. 757-767, Oct. 2008.
• Área do conhecimento: Ciências Biológicas - Bioquímica
• Citações Web of Science: 29
• Assunto(s): Neoplasias renais Análise de sequência com séries de oligonucleotídeos Genes supressores de tumor

Resumo

The clear cell subtype of renal cell carcinoma (RCC) is the most lethal and prevalent cancer of the urinary system. To investigate the molecular changes associated with malignant transformation in clear cell RCC, the gene expression profiles of matched samples of tumor and adjacent non-neoplastic tissue were obtained from six patients. A custom-built cDNA microarray platform was used, comprising 2292 probes that map to exons of genes and 822 probes for noncoding RNAs mapping to intronic regions. Intronic transcription was detected in all normal and neoplastic renal tissues. A subset of 55 transcripts was significantly down-regulated in clear cell RCC relative to the matched nontumor tissue as determined by a combination of two statistical tests and leave-one-out patient cross-validation. Among the down-regulated transcripts, 49 mapped to untranslated or coding exons and 6 were intronic relative to known exons of protein-coding genes. Lower levels of expression of SIN3B, TRIP3, SYNJ2BP and NDE1 (P < 0.02), and of intronic transcripts derived from SND1 and ACTN4 loci (P < 0.05), were confirmed in clear cell RCC by Real-time RT-PCR. A subset of 25 transcripts was deregulated in additional six nonclear cell RCC samples, pointing to common transcriptional alterations in RCC irrespective of the histological subtype or differentiation state of the tumor. Our results indicate a novel set of tumor suppressor gene candidates, including noncoding intronic RNAs, which may play a significant role in malignant transformations of normal renal cells. (AU)

• Processo FAPESP: 02/13283-6 - Identificação de marcadores moleculares para diagnóstico e prognóstico em câncer utilizando microarrays de DNA
• Beneficiário: Sergio Verjovski Almeida
• Modalidade de apoio: Auxílio à Pesquisa - Temático