Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA342847 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The clearance of oxidative stress compounds is critical for the protection of the organism from malignancy, but how this key physiological process is regulated is not fully understood. Here we found that the expression of GPRC5A, a well-characterized tumor suppressor in lung cancer, was elevated in colorectal cancer tissues in patients. In both cancer cell lines and a colitis-associated cancer model in mice, we found that GPRC5A deficiency reduced cell proliferation and increased cell apoptosis as well as inhibited tumorigenesis in vivo. Through RNA-Seq transcriptome analysis, we identified oxidative stress associated pathways were dysregulated. Moreover, in GPRC5A deficient cells and mouse tissues, the oxidative agents were reduced partially due to increased glutathione (GSH) level. Mechanistically, GPRC5A regulates NF-κB mediated Vanin-1 expression which is the predominant enzyme for cysteamine synthesis. Administration of cystamine (the disulfide form of cysteamine) in GPRC5A deficient cell lines inhibited γ-GCS activity leading to restoration of GSH level and increase of cell growth. Taken together, our studies suggest that GPRC5a is a potential biomarker for colon cancer and promotes tumorigenesis through stimulation of Vanin-1 expression and oxidative stress in colitis associated cancer. This study revealed an unexpected oncogenic role of GPRC5A in colorectal cancer suggesting there are complicated functional and molecular mechanism differences of this gene in distinct tissues.
2016-09-14 | GSE86895 | GEO
Project description:Metabolic remodeling is a strategy for tumor to survival under stress and identifying the key genes driving the metabolic remodeling of colorectal cancer (CRC) and understanding its mechanisms may provide new targets for tumor intervention. Melanocyte proliferating gene 1 (MYG1) is a 3'-5' RNA exonuclease and plays key role in mitochondrial functions. Here, we uncover that MYG1 expression is upregulated in CRC progression and highly expressed MYG1 promotes glycolysis and CRC progression independent of its exonuclease acitvity through nuclear-mitochondrial collaboration.
2023-12-01 | GSE241878 | GEO
Project description:Oxidative stress plays a critical role in liver tissue damage and in hepatocellular carcinoma (HCC) initiation and progression. However, the mechanisms that regulate autophagy and metabolic reprogramming during the generation of reactive oxygen species (ROS), and how ROS promotes tumorigenesis, still need to be fully understood. We show that protein kinase C (PKC) / loss in hepatocytes promotes autophagy and oxidative phosphorylation. This results in ROS generation, which through NRF2 drives HCC cell autonomously and non-autonomously. Although PKC / promotes tumorigenesis in oncogene-driven cancer models, emerging evidence demonstrate that it is a tumor suppressor in more complex carcinogenic processes. Consistently, PKC / levels negatively correlate with HCC histological tumor grade, establishing this kinase as a tumor suppressor in liver cancer.
2020-06-30 | GSE147800 | GEO
Project description:Oxidative stress plays a critical role in liver tissue damage and in hepatocellular carcinoma (HCC) initiation and progression. However, the mechanisms that regulate autophagy and metabolic reprogramming during the generation of reactive oxygen species (ROS), and how ROS promotes tumorigenesis, still need to be fully understood. We show that protein kinase C (PKC) / loss in hepatocytes promotes autophagy and oxidative phosphorylation. This results in ROS generation, which through NRF2 drives HCC cell autonomously and non-autonomously. Although PKC/ promotes tumorigenesis in oncogene-driven cancer models, emerging evidence demonstrate that it is a tumor suppressor in more complex carcinogenic processes. Consistently, PKC / levels negatively correlate with HCC histological tumor grade, establishing this kinase as a tumor suppressor in liver cancer.
2020-06-30 | GSE147778 | GEO
Project description:The Notch signaling pathway regulates fate decision, proliferation and differentiation of intestinal epithelial cells. However, the role of Notch signaling in colorectal cancer progression is largely unknown. Here we show that Notch signaling suppresses the progression of colorectal tumorigenesis, even though it augments tumor initiation. In contrast to adenomas of Apcmin mice, Notch-inactivated Apcmin adenomas showed more malignant characteristics, such as submucosal invasion and loss of glandular pattern. Conversely, Notch-activated Apcmin adenomas showed a reversion from high-grade to low-grade features, such as the restoration of adherent junctions. Expression profiling revealed that Notch signaling promotes the differentiation of tumor cells with down regulation of Wnt/beta-catenin target genes and inhibition of epithelial-mesenchymal transition. Comparison of mouse and human expression profiles also suggests the common role of Notch in inhibition of tumor progression. Interestingly, Notch signaling suppressed the expression of beta-catenin responsive genes through chromatin modification of Tcf4/beta-catenin binding sides. Our results suggest that Notch signaling has dual roles in colorectal tumorigenesis: promoting adenoma initiation, while inhibiting tumor progression to colorectal cancer. mRNAs from normal (WT, Notch-activated and Notch-inactivated) and tumor (WT, Notch-activated and Notch-inactivated) tissues were profiled.
2011-04-19 | E-GEOD-21392 | biostudies-arrayexpress
Project description:Increasing the understanding of the impact of changes in oncogenes and tumor suppressor genes is essential for improving the management of lung cancer. Recently, we identified a new mouse lung-specific tumor suppressor - the G-protein coupled receptor 5A (Gprc5a). We sought to understand the molecular consequences of Gprc5a loss and towards this we performed microarray analysis of the transcriptomes of lung epithelial cells cultured from normal tracheas of Gprc5a knockout and wild-type mice to define a loss-of-Gprc5a gene signature. Gprc5a wild type cells (WT-NLE) and Gprc5a knockout cells (NULL-NLE) were isolated and cultured from trachea of three week old Gprc5a wild type and knockout mice, respectively. Following RNA extraction and purification, the transcriptome of the Gprc5a wild type and knockout cells were analyzed by microarray analysis using the Affymetrix MG-430 2.0 murine array platform.
2010-04-13 | E-GEOD-21309 | biostudies-arrayexpress
Project description:To investigate the function of GPRC5A and aromatic monoamine, we generated GPRC5A knock-out HT-29 colorectal cancer cells by CRISPR-Cas9 gene editing and evaluated changes in gene expression by RNA sequencing. Wild-type and GPRC5A knock-out cells revealed significant differences in gene expression patterns, particularly the immune- and cancer-related genes. The regulation of gene expression by GPRC5A is not significantly affected by 7-fluorotryptamine and/or TNFa.
2023-02-20 | GSE225392 | GEO
Project description:Gprc5a is a lung tumor suppressor gene. Gprc5a-knockout (ko) mice can develop spontaneous lung cancer and Gprc5a-ko mouse model is relevant to human lung cancer. Thus, exploration of the mechanisms underlying lung tumorigenesis in Gprc5a-ko mice would be very helpful for revealing those in human lung cancer. We used microarrays to detail the global gene expression profile that underlies oncogenesis by Gprc5a-knockout gene deletion in mouse tracheal epithelial cells. Wild type and gene-knockout mouse tracheal epithelial cells that were divided into two groups were used for RNA extraction.
2013-10-29 | E-GEOD-51777 | biostudies-arrayexpress
Project description:Age-induced methylmalonic acid accumulation promotes tumor progression
| PRJNA524129 | ENA
Project description:The Notch signaling pathway regulates fate decision, proliferation and differentiation of intestinal epithelial cells. However, the role of Notch signaling in colorectal cancer progression is largely unknown. Here we show that Notch signaling suppresses the progression of colorectal tumorigenesis, even though it augments tumor initiation. In contrast to adenomas of Apcmin mice, Notch-inactivated Apcmin adenomas showed more malignant characteristics, such as submucosal invasion and loss of glandular pattern. Conversely, Notch-activated Apcmin adenomas showed a reversion from high-grade to low-grade features, such as the restoration of adherent junctions. Expression profiling revealed that Notch signaling promotes the differentiation of tumor cells with down regulation of Wnt/beta-catenin target genes and inhibition of epithelial-mesenchymal transition. Comparison of mouse and human expression profiles also suggests the common role of Notch in inhibition of tumor progression. Interestingly, Notch signaling suppressed the expression of beta-catenin responsive genes through chromatin modification of Tcf4/beta-catenin binding sides. Our results suggest that Notch signaling has dual roles in colorectal tumorigenesis: promoting adenoma initiation, while inhibiting tumor progression to colorectal cancer.
2011-04-19 | GSE21392 | GEO