Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

IMPDH1/YB-1 Positive Feedback Loop Assembles Cytoophidia and Represents a Therapeutic Target in Metastatic Tumors

ABSTRACT: Recently, cytoophidium, a non-membrane-bound intracellular polymeric structure, has been shown to exist in various organisms, including tumor tissues, but its function and mechanism have not yet been examined. Examination of cytoophidia-assembled gene IMPDH and CTPS mRNA levels showed that only IMPDH1 levels were significantly higher in the clear cell renal cell carcinoma (ccRCC). IMPDH1 was positively correlated with the metastasis-related gene YB-1, and served as an independent prognostic factor in ccRCC. Kaplan–Meier analysis indicated that patients with tumors that expressed high IMPDH1 levels had a shorter overall survival (OS) and disease-free survival (DFS). Furthermore, detection of cytoophidia by immunofluorescence staining in ccRCC tissues showed that IMPDH1-assembled cytoophidia are positively associated with tumor metastasis. Mechanistically, IMPDH1 and YB-1 formed an autoregulatory positive feedback loop: IMPDH1 maintained YB-1 protein stabilization; YB-1 induced IMPDH1 expression by binding to the IMPDH1 promoter motif. Functionally, IMPDH1-assembled cytoophidia physically interacted with YB-1 and translocated YB-1 into the cell nucleus, thus correlating with ccRCC metastasis. Our findings provide the first solid theoretical rationale for targeting the IMPDH1/YB-1 axis to improve metastatic renal cancer treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE146231 | GEO | 2020/03/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Identification of metastasis associated genes in clear cell renal cell carcinoma

Project description:This study investigates the genes that promote clear cell renal cell carcimoma (ccRCC) metastasis using 4 primary metastatic and 5 non-metastatic tumor samples. U133 plus 2.0 array was used to identify the diffrently expressed genes between the primary metastatic and non metastatic ccRCC samples To identify differences in gene expression assoctiated with ccRCC metastasis, 4 primary metastatic and 5 non-metastatic ccRCC samples were used to perform expression profiling.

2013-05-25 | E-GEOD-47352 | biostudies-arrayexpress

piwi-interacting RNA sequencing of 2 paired clear cell renal cell carcinoma tissues and adjacent normal tissues

Project description:Clear cell renal cell carcinoma is one of the most common diagnostic tumor, with nearly one third patients diagnosed as metastatic ccRCC. Although increasing number of studies have revealed that piwi-interacting RNAs were aberrantly expressed in diverse type of cancers, few of them explored the detailed molecular mechanism of piRNAs in carcinogenesis, particular in ccRCC. In this study, differentially expressed piRNAs associated with ccRCC was selected by using piRNA-sequencing combined with analyzing TCGA data, from which piR-57125 was identified. PiR-57125 was found remarkably downregulated in ccRCC samples. Functionally, knockdown of piR-57125 promoted migration and invasion of ccRCC, while overexpression of piR-57125 suppressed ccRCC metastasis. In vivo lung metastasis model also confirmed the same results. CCL3 was identified as the direct target of piR-57125 which could reverse the inhibition effect of piR-57125 in ccRCC metastasis. Further studies revealed that piR-57125 modulated ccRCC metastasis through AKT/ERK pathway. Those data indicate that piR-57125 restrains ccRCC metastasis through directly targeting CCL3 and inhibiting AKT/ERK pathway, and could be a potential therapeutic target for ccRCC.

2021-09-08 | GSE183496 | GEO

Gene expression data from the 786-O renal cell carcinoma cell line and its metastatic derivatives.

Project description:Inactivation of the von Hippel-Lindau tumor suppressor gene, VHL, is an archetypical tumor-initiating event in clear cell renal carcinoma (ccRCC) that leads to the activation of hypoxia-inducible transcription factors (HIFs). However, VHL mutation status in ccRCC is not correlated with clinical outcome. Here we show that during ccRCC progression, cancer cells exploit diverse epigenetic alterations to empower a branch of the VHL-HIF pathway for metastasis, and the strength of this activation is associated with poor clinical outcome. By analyzing metastatic subpopulations of VHL-deficient ccRCC cells, we discovered an epigenetically altered VHL-HIF response that is specific to metastatic ccRCC. Focusing on the two most prominent pro-metastatic VHL-HIF target genes, we show that loss of polycomb repressive complex 2 (PRC2)-dependent histone H3 Lys27 trimethylation (H3K27me3) activates HIF-driven chemokine (C-X-C motif) receptor 4 (CXCR4) expression in support of chemotactic cell invasion, whereas loss of DNA methylation enables HIF-driven cytohesin 1 interacting protein (CYTIP) expression to protect cancer cells from death cytokine signals. Thus, metastasis in ccRCC is based on an epigenetically expanded output of the tumor-initiating pathway. Gene expression profiles of 786-O renal cell carcinoma cells and metastatic subpopulations isoloated by in vivo selection in immunocomrpmized mice. The derivatives are significantly enriched in the metastatic propensity as measure by experimental metastasis assays.

2012-12-05 | E-GEOD-32295 | biostudies-arrayexpress

Apolipoprotein L1 is a tumor suppressor in clear cell renal cell carcinoma metastasis [miRNA-Seq]

Project description:The 5-year survival rate of kidney cancer drops dramatically from 93% to 15% when it is metastatic. Metastasis constitutes for 30% of kidney cancer cases, in which clear cell renal cell carcinoma (ccRCC) is the most prominent subtype. By sequencing mRNA of ccRCC patient samples, we found that apolipoprotein L1 (APOL1) was highly expressed in tumors compared to their adjacent normal tissues. This gene has been previously identified in a large body of kidney disease research and was reported as a potential prognosis marker in many types of cancers. However, the molecular function of APOL1 in ccRCC, especially in metastasis, remained unknown. In this study, we modulated the expression of APOL1 in various renal cancer cell lines and analyzed their proliferative, migratory, and invasive properties. Strikingly, APOL1 overexpression suppressed ccRCC metastasis both in vitro and in vivo. We then explored the mechanism by which APOL1 alleviated ccRCC malignant progression by investigating its downstream pathways. APOL1 overexpression diminished the activity of focal adhesive molecules, Akt signaling pathways, and EMT processes. Furthermore, in the upstream, we discovered that miR-30a-3p could inhibit APOL1 expression. In conclusion, our study revealed that APOL1 play a role as a tumor suppressor in ccRCC and inhibit metastasis, which may provide novel potential therapeutic approaches for ccRCC patients.

2024-04-10 | GSE252629 | GEO

Apolipoprotein L1 is a tumor suppressor in clear cell renal cell carcinoma metastasis [RNA-Seq]

2024-04-10 | GSE252600 | GEO

Identification of metastasis associated genes in clear cell renal cell carcinoma

2013-05-25 | GSE47352 | GEO

H3K27ac and BRD4-binding regions in a clear cell renal cell carcinoma cell line, OS-RC-2

Project description:Advanced clear cell renal cell carcinoma (ccRCC) frequently causes systemic inflammation. Here, we identified the functional role and regulatory mechanism of inflammation driven by advanced ccRCC cells. The inflammatory nature of advanced ccRCC was recapitulated in a preclinical model of ccRCC. Amplification of cancer cell-intrinsic inflammation during ccRCC progression triggered neutrophil-dependent lung metastasis. Massive expression of inflammation-related genes was transcriptionally activated by epigenetic remodelling through mechanisms such as DNA demethylation and super-enhancer formation. Bromodomain and extra-terminal motif inhibitor (BETi) synchronously suppressed C–X–C-type chemokines in ccRCC cells and decreased neutrophil-dependent lung metastasis. Overall, our findings shed insight into the nature of inflammatory ccRCC, which triggers metastatic cascades, and suggest a potential therapeutic strategy.

2020-10-28 | GSE131139 | GEO

RNA-sequencing of neutrophils derived from OS-RC-2-bearing mice

2020-10-28 | GSE131138 | GEO

RNA-sequencing of a clear cell renal cell carcinoma cell line, OS-RC-2

2020-10-28 | GSE131137 | GEO

Single-cell analysis of immune and stroma cell remodeling in renal cell carcinoma primary tumors and bone metastatic lesions

Project description:Cancer metastasis in the bone represents an incurable disease. About one-third of patients with advanced renal cell carcinoma (ccRCC) have bone metastasis at the time of diagnosis making it a life-threatening disease. The bone metastatic niche, including immune and stroma microenvironment, has not been defined. Here, we created a human single-cell transcriptome cell-atlas of ccRCC bone metastases, contrasted with normal bone marrow immune cells and stroma.

2023-07-17 | GSE202813 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data