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The RNF26/CBX7 axis modulates the TNF signaling pathway to promote cell proliferation and regulate sensitivity to TKIs in ccRCC

ABSTRACT: We performed CBX7 knockdown in renal cancer cells along with RNA sequencing. The expression profiling showed TNF signaling as a potential CBX7 target and the conditions were also verified in clinical samples.

ORGANISM(S): Homo sapiens

PROVIDER: GSE185630 | GEO | 2022/10/11

REPOSITORIES: GEO

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The RNF26/CBX7 axis modulates the TNF signaling pathway to promote cell proliferation and regulate sensitivity to TKIs in ccRCC

Project description:The RNF26/CBX7 axis modulates the TNF signaling pathway to promote cell proliferation and regulate sensitivity to TKIs in ccRCC

| PRJNA770196 | ENA

Polycomb CBX7 represses expression of tumor suppressor genes

2009-09-23 | GSE10541 | GEO

Polycomb CBX7 represses expression of tumor suppressor genes

Project description:Polycomb CBX7 was stably expressed in embryonal carcinoma cells in order to identify target genes. The study was specifically geared toward unveiling gene targets that are susceptible to DNA hypermethylation in adult cancer. A number of CBX7 target tumor suppressor genes were thereby identified and used in further studies to characterize the mechanism surrounding CBX7 mediated gene suppression. Keywords: CBX7 target gene identification A cDNA encoding the ORF of polycomb CBX7 under the control of EF1alpha promoter was transfected into the Tera-2 embryonal carcinoma cell line. Empty vector was used to transfect control cells. The cells were subject to stable selection using puromycin and a pooled population of CBX7 overexpressing cells was established. Gene expression analysis was performed by comparing the gene expression profile of CBX7 cells to empty vector control cells.

2009-09-23 | E-GEOD-10541 | biostudies-arrayexpress

Genes regulated by CBX7

Project description:We analyzed the expression profile of a thyroid carinoma cell line after the restoration of CBX7 expression.

2014-06-01 | E-MTAB-2420 | biostudies-arrayexpress

Consequence of knock down of CBX7 in multiple cell lines

Project description:We conduct an experiment where CBX7 is knocked down in 4 different cell lines: A549, H1299, K562 and THP-1. After culturing these cell lines for three days with or without knockdown of CBX7, we then perform RNA sequencing (RNA-seq) to assess the impact.

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Transcriptome profiling after CBX7 knockdown in LNCaP cells

Project description:An analysis of transcriptomal changes upon knockdown of CBX7 in prostate cancer LNCaP cells.

2017-07-05 | E-MTAB-3730 | biostudies-arrayexpress

Transcriptome Analysis of Cbx7 Knockdown Effects in Ovarian Clear Cell Adenocarcinoma Cell Lines

Project description:Cbx7 knockdown resulted in increase of genes related with apoptosis and inflammation. Expression microarray was performed using RNA extracted from 2 ovarian clear cell adenocarcinoma cell lines, namely, KOC-7C and TOV21G, either trancduced by Cbx7 siRNA or control.

2013-11-01 | E-GEOD-47146 | biostudies-arrayexpress

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OTUD1 stabilizes PTEN to inhibit the PI3K/AKT and TNF-alpha/NF-kappaB signaling pathways and sensitize ccRCC to TKIs.

Project description:Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma and has the highest mortality rate. For metastatic RCC, systemic drug therapy is the most important method in addition to surgical tumor reduction. In recent years, tyrosine kinase inhibitors (TKIs) targeting the angiogenesis have been applied to treat ccRCC and achieved profound therapeutic effects. It has been reported that most patients receiving antiangiogenic therapy will develop resistance within 15 months. The mechanism of resistance to targeted therapy is extremely complex and has not been clarified. Ovarian tumor-associated protease domain-containing proteins (OTUDs) belonging to DUBs play a critical role in the tumorigenesis of solid tumors. However, the specific role of OTUDs in ccRCC is still elusive. Here, we investigated the clinicopathological role of OTUD family members in ccRCC. We demonstrated that OTUD1 was downregulated in renal cancer and involved in the poor prognosis of renal cancer. Then, we showed that OTUD1 inhibits cancer cell growth. Moreover, analysis of OTUD1 RNA-seq data indicated that OTUD1 inhibition triggers the AKT and NF-kappa B pathways in renal cancer cells. Furthermore, OTUD1 interacts with PTEN and regulates its stability. Subsequently, we revealed that downregulation of OTUD1 contributes to the sensitivity of renal cancer cells to TKIs, and this effect was blocked by TNF/NF-kappa B inhibitors and AKT inhibitors. Thus, we identified that the OTUD1-PTEN axis suppresses tumor growth and regulates the resistance of renal cancer to TKIs.

| S-EPMC8898358 | biostudies-literature

Denaturing CLIP (dCLIP) pipeline identifies discrete RNA footprints on chromatin-associated proteins and reveals that CBX7 targets 3’UTRs to regulate mRNA expression

Project description:Interaction networks between chromatin complexes and long noncoding RNAs have become a recurrent theme in epigenetic regulation. However, technical limitations have precluded identification of RNA binding motifs for chromatin-associated proteins. Here we add a denaturation step to UV-crosslink RNA immunoprecipitation (dCLIP), and apply dCLIP to mouse and human chromobox homolog 7 (CBX7), an RNA-binding subunit of Polycomb repressive complex 1 (PRC1). In both species, CBX7 predominantly binds 3’ untranslated regions (UTRs) of messenger RNAs. CBX7 binds with a median RNA “footprint” of 171-183 nucleotides, the small size of which facilitates motif identification by bioinformatics. We find four families of consensus RNA motifs in mouse, and independent analysis of human CBX7 dCLIP data identifies similar motifs. Their mutation abolishes CBX7 binding in vitro. Pharmacological intervention with antisense oligonucleotides paradoxically increases CBX7 binding and enhances gene expression. These data support the utility of dCLIP and reveal an unexpected functional interaction between CBX7 and the 3’UTRs of mRNA.interacts with a range of transcripts, it predominantly binds 3’ untranslated regions (UTRs) of messenger RNAs. CBX7 has a median RNA “footprint” of 171 nucleotides, enabling identification of four families of motifs that tend to co-cluster in the 3’UTR. Manipulating the CBX7-3’UTR interactions and motifs with antisense oligonucleotides results in upregulation of mRNA and protein expression, thereby validating the dCLIP method and revealing functional interactions between CBX7 and mRNA.

2017-10-25 | GSE88823 | GEO

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