Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1164393 | ENA |
REPOSITORIES: ENA
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Project description:SCN5A was reported to promote proliferation and invasiveness potential in colorectal cancer, yet the mechanism was not clarified, and little was known about its association with chemosensitivity to 5-fluorouracil. In the current study, elevated SCN5A expression were associated with poor prognosis and metastasis in colorectal cancers, whereas stage II-III patients with up-regulated SCN5A expression were more likely to benefit from 5-fluorouracil-based adjuvant chemotherapy. SCN5A could promote proliferation and invasiveness potential through regulating cell cycle and epithelial-mesenchymal transition in colorectal cancer cells. Furthermore, SCN5A regulated Ras signaling by stabilizing KRas-calmodulin complex through Ca2+ influx. Apart from that, under 5-fluorouracil treatment, SCN5A promoted calmodulin-dependent apoptosis in colorectal cancers.
2020-05-09 | GSE150134 | GEO
Project description:We analyzed the differentially regulated genes in 5-fluorouracil-resnstant human colon cancer cells to discover novel biomarkers involved in 5-FU resistance in colorectal cancer.
2017-03-27 | GSE56322 | GEO
Project description:The radio-chemotherapy with 5-fluorouracil (5-FU) is the standard of care treatment for patients with locally advanced rectal cancer (LARC) but it is only effective for a third of them. The proteomic and transcriptomic response of three colorectal cancer (CRC) cell lines to 5-FU and radiation was assessed and correlated with their genetic background. The induction of a 5-FU-resistance in those cell lines negatively affects the levels of transcripts corresponding to Krüppel-associated box (KRAB)-containing zinc finger proteins (ZFPs), the largest family of transcriptional repressors. Among nearly 350 KRAB-ZFPs, almost a quarter are down-regulated after the induction of a 5-FU-resistance including a common one between the three CRC cell lines, ZNF649, whose role is still unknown. This proteomic, transcriptomic and genomic analysis of intrinsic and acquired resistance highlights possible new mechanisms involved in resistance to treatment and therefore potential new therapeutic targets to overcome this resistance.
2022-05-19 | PXD020000 | Pride
Project description:Glioblastoma (GBM) is a lethal brain cancer exhibiting high levels of drug resistance, a feature partially imparted by tumor cell stemness. Recent work shows that homozygous MTAP deletion, a genetic alteration occurring in about half of all GBMs, promotes stemness in GBM cells. Exploiting MTAP loss-conferred deficiency in purine salvage, we demonstrate that purine synthesis blockade via treatment with L-Alanosine (ALA), an inhibitor of de novo purine synthesis, attenuates stemness and mitochondrial function of MTAP-deficient GBM cells. Here, we use RNA-Seq with ALA-treated patient-derived GBM cells to investigate the transcriptomic impact of long-term ALA treatment.
2022-04-27 | GSE197728 | GEO
Project description:Abstract The aggressive nature and poor prognosis of lung cancer led us to explore the mechanisms driving disease progression. Utilizing our invasive cell-based model, we identified methylthioadenosine phosphorylase (MTAP) and confirmed its suppressive effects on tumorigenesis and metastasis, and patients with low MTAP expression displayed worse overall and progression-free survival. Mechanistically, accumulation of methylthioadenosine substrate in MTAP-deficient cells reduced the level of protein arginine methyltransferase 5 (PRMT5)-mediated symmetric dimethylarginine (sDMA) modification on proteins. Vimentin was revealed as a novel dimethyl-protein with less dimethylation level in response to MTAP loss. The sDMA modification on vimentin reduces its protein abundance and trivially affects its filamentous structure. In MTAP-loss cells, lower sDMA level prevents ubiquitination-mediated vimentin degradation, thereby stabilizing vimentin, contributing to cell invasion. This inverse association of the MTAP/PRMT5 axis with vimentin proteins was clinically corroborated. Taken together, we propose a novel mechanism of vimentin post-translational regulation and provide new insights in metastasis.
2022-05-31 | PXD031192 | Pride
Project description:Despite advances in the detection and management of colorectal cancers, resistance to anti-cancer therapies remains a significant challenge. Activating mutations in KRAS and BRAF are frequently observed in colorectal cancers and have been associated with aggressive tumors and poor survival after chemotherapy. In the present study, we demonstrate that mutations in KRAS/BRAF alter the enhancer landscape of tumor cells, which leads to the resistance of the cornerstone colorectal cancer chemotherapeutic agent 5-fluorouracil (5-FU) through activation of transcription factor GATA1. Targeted inhibition of GATA1 reverses epigenetic changes in KRAS mutant cells and restores sensitivity to 5-FU. These results indicate a novel therapeutic opportunity for tailoring individualized therapy in human colorectal cancer.
2019-10-01 | GSE115400 | GEO
Project description:The radio-chemotherapy with 5-fluorouracil (5-FU) is the standard of care treatment for patients with locally advanced rectal cancer (LARC) but it is only effective for a third of them. The proteomic and transcriptomic response of three colorectal cancer (CRC) cell lines to 5-FU and radiation was assessed and correlated with their genetic background. The induction of a 5-FU-resistance in those cell lines negatively affects the levels of transcripts corresponding to Krüppel-associated box (KRAB)-containing zinc finger proteins (ZFPs), the largest family of transcriptional repressors. Among nearly 350 KRAB-ZFPs, almost a quarter are down-regulated after the induction of a 5-FU-resistance including a common one between the three CRC cell lines, ZNF649, whose role is still unknown. This proteomic, transcriptomic and genomic analysis of intrinsic and acquired resistance highlights possible new mechanisms involved in resistance to treatment and therefore potential new therapeutic targets to overcome this resistance.
2022-04-13 | GSE153412 | GEO
Project description:Hepatocyte-nuclear-factor-4? (??Hnf4?) is a transcription factor that controls epithelial cell polarity and maturation during embryogenesis. Hnf4? conditional deletion during post-natal development results in minor consequences on intestinal epithelium integrity but promotes activation of the Wnt/?-catenin pathway. Here we show that Hnf4? does not act as a tumor suppressor gene but is crucial to promote gut tumorigenesis in mice. Polyp multiplicity in ApcMin mice that lacks Hnf4? is suppressed in comparison to littermate ApcMin controls. Analysis of microarray gene expression profiles from mice lacking Hnf4? in the intestinal epithelium identifies its novel function in regulating the expression of reactive oxygen species (ROS) detoxifying genes. This role is supported with the demonstration that HNF4? is functionally involved in the protection against spontaneous and 5-fluorouracil chemotherapy-induced production of intracellular ROS in colorectal cancer cell lines. The analysis of a colorectal cancer patient cohort establishes that HNF4? is significantly up-regulated at both gene transcript and protein levels in tumors relative to adjacent benign epithelial resections. Several genes involved in ROS neutralization are also up-regulated in correlation with HNF4? expression. All together, the findings point to the nuclear receptor HNF4? as a potential therapeutic target to eradicate aberrant epithelial cell resistance to ROS production during intestinal tumorigenesis. HNF4alpha was conditionally knockout in the mouse epithelial intestine with the 12.4-kb VillinCRE. A total of 3 control and 3 mutant littermates individuals were sacrificed at 7 months of age. The distal jejunum was harvested and Total RNA was isolated from each individuals. Each RNA sample was independently used to generate probes to screen affymetrix chips.
2011-01-01 | E-GEOD-20968 | biostudies-arrayexpress