Transcriptomics

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Expression analysis and in silico characterization of intronic long noncoding RNAs in renal cell carcinoma: emerging functional associations (RCC expression)


ABSTRACT: Intronic and intergenic long noncoding RNAs (lncRNAs) are emerging gene expression regulators. The molecular pathogenesis of renal cell carcinoma (RCC) is still poorly understood, and in particular, limited studies are available for intronic lncRNAs expressed in RCC. Microarray experiments were performed with two different custom-designed arrays enriched with probes for lncRNAs mapping to intronic genomic regions. Samples from 18 primary clear cell RCC tumors and 11 nontumor adjacent matched tissues were analyzed with 4k-probes microarrays. Oligoarrays with 44k-probes were used to interrogate 17 RCC samples (14 clear cell, 2 papillary, 1 chromophobe subtypes) split into four pools. Meta-analyses were performed by taking the genomic coordinates of the RCC-expressed lncRNAs, and cross-referencing them with microarray expression data from three additional human tissues (normal liver, prostate tumor and kidney nontumor samples), and with large-scale public data for epigenetic regulatory marks and for evolutionarily conserved sequences. A signature of 29 intronic lncRNAs differentially expressed between RCC and nontumor samples was obtained (false discovery rate (FDR) <5%). An additional signature of 26 intronic lncRNAs significantly correlated with the RCC five-year patient survival outcome was identified (FDR <5%, p-value ≤0.01). We identified 4303 intronic antisense lncRNAs expressed in RCC, of which 25% were cis correlated (r >|0.6|) with the expression of the mRNA in the same locus across three human tissues. Gene Ontology (GO) analysis of those loci pointed to ‘regulation of biological processes’ as the main enriched category. A module map analysis of all expressed protein-coding genes in RCC that had a significant (r ≥|0.8|) trans correlation with the 20% most abundant lncRNAs identified 35 relevant (p <0.05) GO sets. In addition, we determined that 60% of these lncRNAs are evolutionarily conserved. At the genomic loci containing the intronic RCC-expressed lncRNAs, a strong association (p <0.001) was found between their transcription start sites and genomic marks such as CpG islands and histones methylation and acetylation. Intronic antisense lncRNAs are widely expressed in RCC tumors. Some of them are significantly altered in RCC in comparison with nontumor samples. The majority of these lncRNAs is evolutionarily conserved and possibly modulated by epigenetic modifications. Our data suggest that these RCC lncRNAs may contribute to the complex network of regulatory RNAs playing a role in renal cell malignant transformation. Tumor kidney tissue samples expression was measured with a 44k-element oligo-array (GPL4051) using 4 pools of tumor samples from 17 RCC patients (14 clear cell RCC, 2 papillary RCC and 1 chromophobe RCC). Pools were obtained from equal amounts of 300ng of DNase-treated total RNA of each tissue sample.

ORGANISM(S): Homo sapiens  

SUBMITTER: Ana C Tahira  Sergio Verjovski-Almeida   Giselle M Vignal   Etel R Gimba   Angela A. Fachel   Eduardo M Reis   Franz S Campos   Vinicius Maracaja-Coutinho   Angela A Fachel   Santiago A Vilella-Arias    

PROVIDER: E-GEOD-40913 | ArrayExpress | 2014-01-21

SECONDARY ACCESSION(S): GSE40913PRJNA175342

REPOSITORIES: GEO, ArrayExpress

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Expression analysis and in silico characterization of intronic long noncoding RNAs in renal cell carcinoma: emerging functional associations.

Fachel Angela A AA   Tahira Ana C AC   Vilella-Arias Santiago A SA   Maracaja-Coutinho Vinicius V   Gimba Etel R P ER   Vignal Giselle M GM   Campos Franz S FS   Reis Eduardo M EM   Verjovski-Almeida Sergio S  

Molecular cancer 20131115 1


BACKGROUND: Intronic and intergenic long noncoding RNAs (lncRNAs) are emerging gene expression regulators. The molecular pathogenesis of renal cell carcinoma (RCC) is still poorly understood, and in particular, limited studies are available for intronic lncRNAs expressed in RCC. METHODS: Microarray experiments were performed with custom-designed arrays enriched with probes for lncRNAs mapping to intronic genomic regions. Samples from 18 primary RCC tumors and 11 nontumor adjacent matched tissues  ...[more]

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