Effect of IL1β on A498 ccRCC cell lines
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA847948 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Renal cell carcinoma is highly inflamed and tumor cells are embedded into a microenvironment enriched of IL1. While inflammatory pathways are well characterized in the immune system, less is known about these same pathways in epithelial cells; it is unclear if and how innate immune signals directly impact on cancer cells, and if we could we manipulate these for therapeutic purpose. To address these questions, we first focused on the inflammatory receptors belonging to the IL1- and Toll-like receptors family including negative regulators in a small cohort of 12 clear cell RCC (ccRCC) patients’ samples as compared to their coupled adjacent normal tissues. Our data demonstrated that renal epithelial cancer cells showed a specific and distinctive pattern of inflammatory receptors expression marked by a consistent downregulation of the inhibitory receptor SIGIRR mRNA. This repression was confirmed at the protein level in both cancer cell lines and primary tissues. When we analyzed in silico data of different kidney cancer histotypes, we identified the clear cell subtype as the one where SIGIRR was mostly downregulated; nonetheless, papillary and chromophobe tumor types also showed low levels as compared to their normal counterpart. RNA-sequencing analysis demonstrated that IL1 stimulation of the ccRCC cell line A498 triggered an intrinsic signature of inflammatory pathways activation characterized by the induction of distinct “pro-tumor” genes including several chemokines, the autocrine growth factor IL6, the atypical co-transcription factor NFKBIZ and the check-point inhibitor PD-L1. When we looked for the macroareas most represented among the differentially expressed genes, additional clusters emerged including pathways involved in cell differentiation, angiogenesis and wound healing. To note, SIGIRR over-expression in A498 cells dampened IL1 signaling as assessed by a reduced induction of NFKBIZ, IL6 and PD-L1. Our results suggest that SIGIRR downregulation unleashes IL1 signaling intrinsic to tumor cells and that manipulating this pathway may be beneficial in ccRCC.
2022-06-13 | GSE205851 | GEO
Project description:HIF-2alpha is essential for (VHL-/-) ccRCC subcutaneous tumor growth in mice, and in tumor cell lines, its inhibition results in increased ROS accumulation, tumor cell death and responsiveness to radiation treatment. We have utilized transcriptional profiling to screen for putative HIF-2alpha targets genes that serve an anti-oxidant and, thus, cell survival function. A498 ccRCC cell line was treated with control siRNA or mixture of two HIF-2alpha specific siRNA for 48 hours, and RNA was harvested. 4 independent experiments were performed, and expression was compared between control and HIF-2alpha knockdown groups.
2009-08-27 | GSE16622 | GEO
Project description:HIF-2alpha is essential for (VHL-/-) ccRCC subcutaneous tumor growth in mice, and in tumor cell lines, its inhibition results in increased ROS accumulation, tumor cell death and responsiveness to radiation treatment. We have utilized transcriptional profiling to screen for putative HIF-2alpha targets genes that serve an anti-oxidant and, thus, cell survival function. A498 ccRCC cell line was treated with control siRNA or mixture of two HIF-2alpha specific siRNA for 48 hours, and RNA was harvested. 4 independent experiments were performed, and expression was compared between control and HIF-2alpha knockdown groups. 8 total samples were applied to Affymetrix Human Gene 1.0 ST Arrays. We performed two-class paired analysis using Significance Analysis of Microarrays (SAM) software to compare expression in the CT (control siRNA) and H2 (Hif2-alpha siRNA) groups.
2009-08-27 | E-GEOD-16622 | biostudies-arrayexpress
Project description:The aim of this study was to compare effect of everolimus on growth of different renal cell carcinoma (RCC) populations and develop design for experiments to measure the early response of everolimus in clear cell RCC (ccRCC) cell lines including renal cancer stem cells. Gene expression profiling using microarray was performed to determine the early response to everolimus after 3 days of treatment with optimizied concentration of drug in two ccRCC cell lines 1) parental clear cell renal cell carcinoma ccRCC-PCSC (HKPCSC -human parental kidney cancer stem cells) and 2) ccRCC-CSC - clear cell renal cell carcinoma -cancer stem cells (HKCSC - human kidney cancer stem cells).
2018-05-31 | GSE106819 | GEO
Project description:VHL loss is the most common genetic alteration event in ccRCC, but its effect on epigenetic landscape has not been elucidated previously. By performing histone modifications (H3K27ac, H3K4me1, H3K4me3) from ccRCC cell lines, we describe the genome-wide cis-regulatory landscapes of VHL-deficient ccRCC tumors. We show that ccRCCs exhibit a pervasive gain of enhancers around hypoxic and metabolic transcriptional targets.
2017-08-22 | GSE86087 | GEO
Project description:Set domain-containing 2 (SETD2) is the most frequently mutated gene among all the histone methyltransferases (HMTs) in Clear cell renal cell carcinoma (ccRCC). Loss of function of SETD2 is significantly associated with poor prognosis in patients with ccRCC. A better understanding of the roles of SETD2 played in ccRCC can greatly improve the prognosis and quality of life of patients with kidney cancer. Clear cell renal carcinoma cell A498 were treated with si-SETD2 and si-NC, and the exosomes were extracted.
2021-12-31 | GSE155810 | GEO
Project description:Gene expression profiling was performed in ccRCC cells, which either express both HIF1alpha and HIF2alpha (either naturally or by virtue of induced expression of HIF1alpha) or express HIF2alpha alone (either naturally or by virtue of a HIF1alpha shRNA), to identify genes regulated by HIF1alpha in ccRCC cells. Three H2 cell lines 769P, A498, and SLR24 were stably infected with retrovirus encoding doxycycline-inducible Luciferase (control) or HIF1alpha, and two H1H2 cell lines Caki-2 and SLR25 were stably infected with retroviruses encoding scrambled (control) or HIF1alpha shRNA. Duplicated samples were used for each condition.
2011-12-02 | E-GEOD-27415 | biostudies-arrayexpress
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
2012-11-01 | E-GEOD-34985 | biostudies-arrayexpress
Project description:Effect of everolimus on clear cell renal cell carcinoma (ccRCC) cell lines - parental and stem cells
| PRJNA418126 | ENA
Project description:clariom D and miRNA v4.0 microarray analyses of 786-O, A498 and Caki-1 cells suntinib resistant cell lines and originator cell lines we used intergrated pathway network analysis to identify miRNA-target gene pairs involved in sunitinib resistance.
2021-09-02 | GSE183140 | GEO