Project description:Despite sunitinib contributes to prolong the progression-free survival of metastatic renal cell carcinoma significantly, the universal presence of resistance limits the initial response rate and restricts durable responses. The mechanisms involved in sunitinib resistance vary and need further investigation. We found lncRNA CCAT1 overexpressed in sunitinib resistant cells while declined in the parental cells. Moreover, lncRNA CCAT1 increased significantly in samples with resistance to sunitinib compared to those with responses to sunitinib. Impoverishment of CCAT1 suppressed cell growth and colony formation while triggered apoptosis. Inversely, the ectopic expression of c-Myc reversed the inhibition of cell growth and enhancement of apoptosis by sh-CCAT1. We also verified that anti-apoptosis protein Bcl-2 and Mcl-1 decreased along with the deregulation of CCAT1, whereas the expression of Bcl-2 and Mcl-1 restored in cells those were transfected sh-CCAT1 and c-Myc simultaneously. Apart from the in vitro experiments, we demonstrated that knockdown of CCAT1 boosted response to sunitinib by performing sunitinib-resistant ACHN mouse models. Briefly, lncRNA CCAT1 conferred renal cell carcinoma resistance to sunitinib in a c-Myc-dependent manner, providing novel target for improvement of sunitinib therapy.
Project description:Long non-coding RNAs (lncRNA) play an important role in carcinogenesis, but knowledge of lncRNA expression in renal cell carcinoma is rudimental. We screened 32,183 lncRNA transcripts in malignant and adjacent normal renal tissue and determined dysregulation of approximately 4% of the lncRNA transcripts in clear cell renal cell carcinoma tissue. The distinct changes of lncRNA expression may be used to develop a non-invasive biomarker, because lncRNAs are detectable in bodily fluids. Microarray experiments were performed to determine the expression of 32,183 lncRNA transcripts belonging to 17,512 lncRNAs in 15 corresponding normal and malignant renal tissues
Project description:We used RNA-SEQ technique to detect lncRNAs expression differences in 53 pairs of tumor and adjacent normal tissues of renal papillary cell carcinoma
Project description:We performed a microRNA (miRNA) microarray on 10 metastatic RCC tumors and compared differential miRNA expresison to 19 primary clear cell renal cell carcinomas (ccRCC). We found there were 65 significantly dysregulated miRNAs; 9 miRNAs were significantly upregulated and 56 miRNAs were significantly downregulated in metastatic RCC when compared to primary clear cell renal cell carcinoma.
Project description:Renal cell carcinoma is the most common neoplasm of the adult kidney. A few subtypes of RCC include papillary RCC (pRCC), chromophobe RCC (chRCC) and the benign oncocytoma tumor. In some cases, distinguishing between the RCC subyptes is difficult. We performed a mircroRNA (miRNA) microarray to determine differential miRNA expression between pRCC, chRCC, and oncocytoma. We performed a miRNA microarray on 10 tumor samples of each papillary renal cell carcinoma (pRCC), chromophobe renal cell carcinoma (chRCC), and oncocytoma.
Project description: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 M-bM-^IM-$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 M-bM-^@M-^Xregulation of biological processesM-bM-^@M-^Y as the main enriched category. A module map analysis of all expressed protein-coding genes in RCC that had a significant (r M-bM-^IM-%|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. A total of 16 human renal tumors from clear cell renal cell carcinoma (RCC) patients were evaluated in this study. We compared the expression profiles of tumor samples obtained from patients with clear cell RCC who died as a consequence of the disease versus those alive without disease (5-years follow-up) to evaluate a possible correlation of the lncRNAs with patient survival. The set of clear cell RCC expression profiles was generated using a custom-designed cDNA microarray platform with 4,608 unique elements in replicate (9,216) enriched in gene fragments that map to intronic regions of known human genes (GPL3985).
Project description:Renal cell carcinoma is the most common neoplasm of the adult kidney. A few subtypes of RCC include papillary RCC (pRCC), chromophobe RCC (chRCC) and the benign oncocytoma tumor. In some cases, distinguishing between the RCC subyptes is difficult. We performed a mircroRNA (miRNA) microarray to determine differential miRNA expression between pRCC, chRCC, and oncocytoma.