Project description:To identify a therapeutic candidate target molecule for ccRCC, we analyzed the microRNA (miRNA) expression signatures in ccRCC clinical specimens. 9 matched pair (normal tissue and ccRCC tissue) plus 7 ccRCC tissue were analyzed for miRNA-microarray
Project description:To identify a therapeutic candidate target molecule for ccRCC, we analyzed the microRNA (miRNA) expression signatures in ccRCC clinical specimens.
Project description:Clear cell renal cell carcinomas (ccRCC) are characterized by arm-wide chromosomal alterations. Loss at 14q is associated with disease aggressiveness in ccRCC, which responds poorly to chemotherapeutics. The 14q locus contains one of the largest miRNA clusters in the human genome; however, little is known about the contribution of these miRNAs to ccRCC pathogenesis. In this regard, we investigated the expression pattern of selected miRNAs at the 14q32 locus in TCGA kidney tumors and in ccRCC cell lines. We validated that the miRNA cluster is downregulated in ccRCC (and cell lines) as well as in papillary kidney tumors relative to normal kidney tissues and primary renal proximal tubule epithelial (RPTEC) cells. We demonstrated that agents modulating expression of DNMT1 (e.g., 5-Aza-deoxycytidine) could modulate miRNA expression in ccRCC cell lines. Lysophosphatidic acid (LPA, a Lysophospholipid mediator elevated in ccRCC) not only increased labile iron content but also modulated expression of 14q32 miRNAs. Through an overexpression approach targeting a subset of 14q32 miRNAs (specifically at subcluster A: miR-431, miR-432, miR-127, and miR-433) in 769-P cells, we uncovered changes in cellular viability and claudin-1, a tight junction marker. A global proteomic approach was implemented using these miRNA overexpressing cell lines which uncovered ATXN2 as a highly downregulated target, which has a role in chronic kidney disease pathogenesis. Collectively, these findings support a contribution of miRNAs at 14q32 in ccRCC pathogenesis.
Project description:We used next-generation sequencing technology to characterize mRNA-seq and miRNA-seq of testes and ovaries of Odontobutis potamophila to elucidate the molecular mechanisms of sex determination and differentiation. We were able to find miRNA-mRNA pairs using bioinformatics analysis and miRNA prediction algorithms.
Project description:VHL loss is the most common genetic alteration event in ccRCC, but its effect on epigenetic landscape has not been elucidated previously. We describe the genome-wide cis-regulatory landscapes of VHL-deficient ccRCC tumors by comparing the epigenetic changes in terms of histone modifications (H3K27ac, H3K4me1, H3K4me3) with the transcriptomics profiles in 10 pairs of normal kidney and ccRCC tissues.
Project description:we used next-generation sequencing technology to characterise mRNA-seq and miRNA-seq of control- and hypoxia-treated P. vachelli livers to elucidate the molecular mechanisms of hypoxia adaptation. We were able to find miRNA-mRNA pairs using bioinformatics analysis and miRNA prediction algorithms.
Project description:This SuperSeries is composed of the following subset Series: GSE34979: Array-based CGH analysis of ccRCC derived cell lines GSE34981: miRNA transcript levels in ccRCC-derived cell lines and proximal tubular epithelial cell samples Refer to individual Series
Project description:Despite numerous studies reporting deregulated microRNA (miRNA) and gene expression patterns in clear cell renal cell carcinoma (ccRCC), no direct comparisons have been made to its presumed normal counterpart; the renal proximal epithelial tubular cells (PTEC). The aim of this study was to determine the miRNA expression profiles of ten clear cell renal cell carcinoma-derived cell lines and short-term cultures of PTEC, and to correlate these with their gene expression, and copy-number profiles. Using microarray-based methods, a significantly altered expression level in ccRCC cell lines was observed for 23 miRNAs and 1630 genes. The set of miRNAs with significantly decreased expression levels include all members of the miR-200 family known to be involved in the epithelial to mesenchymal transition (EMT) process. Expression levels of 13 of the 47 validated target genes for the downregulated miRNAs were increased more than two-fold. Our data reinforce the importance of the EMT process in the development of ccRCC. For mRNA expression data of these cell lines see GEO Series accession number GSE20491. MicroRNA profiling was performed on two proximal tubular epithelial cell samples (both cell samples were hybridized twice (biological duplicates)) and ten clear cell renal cell carcinoma- derived cell lines (one of which; RCC-JF in duplicate)
Project description:Despite numerous studies reporting deregulated microRNA (miRNA) and gene expression patterns in clear cell renal cell carcinoma (ccRCC), no direct comparisons have been made to its presumed normal counterpart; the renal proximal epithelial tubular cells (PTEC). The aim of this study was to determine the miRNA expression profiles of ten clear cell renal cell carcinoma-derived cell lines and short-term cultures of PTEC, and to correlate these with their gene expression, and copy-number profiles. Using microarray-based methods, a significantly altered expression level in ccRCC cell lines was observed for 23 miRNAs and 1630 genes. The set of miRNAs with significantly decreased expression levels include all members of the miR-200 family known to be involved in the epithelial to mesenchymal transition (EMT) process. Expression levels of 13 of the 47 validated target genes for the downregulated miRNAs were increased more than two-fold. Our data reinforce the importance of the EMT process in the development of ccRCC. For mRNA expression data of these cell lines see GEO Series accession number GSE20491.
