Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA243562 | ENA |
REPOSITORIES: ENA
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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:Despite the efforts in defining the molecular mechanisms for the drug resistance in colorectal cancers, little is known about the roles of microRNAs. With microarray containing 723 microRNAs, we examined effect of 5-fluorouracil (5-FU) on the microRNA expression. Respond to 5-FU, we identify two microRNAs, miR-19b and miR-21, that were differentially expressed in 5-FU resistant colon cancer cells derived from KM12C and DLD-1.
2011-07-27 | GSE30894 | GEO
Project description:Despite the efforts in defining the molecular mechanisms for the drug resistance in colorectal cancers, little is known about the roles of microRNAs. With microarray containing 723 microRNAs, we examined effect of 5-fluorouracil (5-FU) on the microRNA expression. Respond to 5-FU, we identify two microRNAs, miR-19b and miR-21, that were differentially expressed in 5-FU resistant colon cancer cells derived from KM12C and DLD-1. DLD-1, DLD-1/R, KM12C, and KM12C/R cells were plated at 1 × 105 cells/well. After pre-culture, cells were treated with 60 uM of 5-FU for 72 h. This was the same condition as the analysis of cell cycle. RNAs were collected before (0 h) and after the treatment of 5-FU (72 h).
2011-07-26 | E-GEOD-30894 | biostudies-arrayexpress
Project description:Metastatic human colon carcinoma cell lines LS411N and SW620 were cultured in the presence of increased concentration of 5-FU. The selected stable cell lines (LS411N-5FU-R and SW620-5FU-R) are CD133+ that are resistant to 5-FU. However, FACS-sorted CD133+ cells from LS411N and SW620 are not resistant to 5-FU, suggesting that only a subset of CD133+ cells are 5-FU-resistant colon cancer stem cells. A global gene expression profiling was performed to identify differentiated expressed genes between LS411N-CD133+ cells and LS411N-5FU-R, and between SW620-CD133+ and SW620-5FU-R cells. These differentially expressed genes are potentially responsible for the colon cancer stem cell phenotypes and chemoresistance.
2016-12-20 | GSE76489 | GEO
Project description:In pancreatic cancer the survival rate is low, as the available treatment options usually only extend survival and seldom produce a cure. Drug resistance and disease reoccurrence is the typical reason for death after cancer diagnosis. 5-Fluorouracil (5-FU) is the main chemostatic used in first line therapy. However the majority of the tumors become resistant to treatment. To investigate acquired 5-FU resistance in pancreatic adenocarcinoma, we established chemoresistant monoclonal cell lines from the Panc03.27 cell line by long-term exposure to 5-FU. In addition to increased expression of markers associated with multidrug resistance, the 5-FU resistant clones showed alterations typical of the process of epithelial-to-mesenchymal transition (EMT), including upregulation of mesenchymal markers and increased invasiveness. Microarray analysis revealed the L1CAM pathway as one of the most upregulated pathways in the chemoresistant clones, which was confirmed on RNA and protein levels. Expression of the adhesion molecule L1CAM is associated with a chemoresistant and migratory phenotype of pancreatic cancer. Using esiRNA targeting L1CAM, or by blocking the extracellular part of L1CAM with monoclonal antibodies, we discovered that the increased invasiveness observed in the chemoresistant cells depends on L1CAM. Using esiRNA targeting β-catenin and/or Slug, we discovered that L1CAM expression depends on Slug rather than β-catenin in the 5-FU resistant cells. We demonstrate a functional link between Slug and the expression level of L1CAM in pancreatic cancer cells having undergone EMT following long-term exposure to 5-FU. Our findings provide further insight into the molecular mechanisms leading to a chemoresistant and migratory phenotype in pancreatic cancer cells and indicate the importance of Slug-induced L1CAM in refractory pancreatic cancer. Examination of expression of 5-Fluorouracil (5-FU) Panc03.27 cell line resistant clone versus expression of 5-FU sensitive clones (NT) in 4 replicates per cell lines
2015-08-11 | E-GEOD-58386 | biostudies-arrayexpress
Project description:One of the main obstacles to therapeutic success in colorectal cancer (CRC) is the development of acquired resistance to treatment with drugs such as 5-fluorouracil (5-FU), the most commonly used drug in CRC patients. Whilst some mechanisms of resistance are well-known, it is clear from the stasis in therapy success rate, that much is still unknown. Here a proteomics approach is taken towards identification using 5-FU resistant sublines of human CRC cell lines generated in-house. Using a multiplexed stable isotope labelling with amino acids in cell culture (SILAC) proteomics strategy, the resistant cell lines, and equivalently passaged 5-FU-sensitive cell lines were compared to parent cell lines grown in Heavy medium using 2D liquid chromatography and Orbitrap Fusion™ Tribrid™ Mass Spectrometry analysis.
2024-06-16 | PXD047672 | Pride
Project description:Drug resistance to 5-fluorouracil (5-FU) and recurrence after chemotherapy in colorectal cancer remain a challenge to be resolved for the improvement of patient outcomes. In the present study, we found that the application of conditioned medium (CM) derived from 5-FU-resistant colon cancer cells HCT-8/FU reduced the chemosensitivity of native HCT-8 to 5-FU, which was accompanied with the significant changes at number counts and morphology of Cajal bodys (CBs), a spherical nuclear body, dynamic exchanging constituent macromolecules (i.e., body-specific proteins and RNAs) with the nucleoplasmic space.It was shown that the disassembly and reassembly of CBs regulated by the phosphorylation of coilin, which was significantly activated by UHMK1. These led to a large number of variations of RNA alternative splicing in cells, which could contribute to the cell survival through remodeling of intracellular phenotype and transmitting preadaptive signal to adjacent cells in tumor microenvironment.
2021-03-15 | GSE168888 | GEO
Project description:We have determined that verticillin A is a histone methyltransfease inhibitor that selectively inhibits human SUV39H1, SUV39H2, G9a and GLP to inhibit H3K9 methylation in human colon cancer cells. The objective here is to identify verticillin A target genes in human colon cancer cells. 5-FU-resistant human colon carcinoma cell lines LS411N-5FU-R was established from the metastatic human colon carcinoma cell line LS411N. LS411N-5FU-R cells were cultured in the absence or presence of verticillin A (50 nM) for 3 days and used for RNA lsolation. DNA microarray analysis was done in replicates in the Georgia Regents University Cancer Center Genomic Core Facility.
2015-04-01 | E-GEOD-51262 | biostudies-arrayexpress
Project description:Metastasis and drug-resistance are major problems in cancer chemotherapy. The purpose of this work was to analyze the molecular mechanisms underlying the invasive potential of drug-resistant colon carcinoma cells. Cellular models included the parental HT-29 cell line and its drug-resistant derivatives selected after chronic treatment with either 5-fluorouracil (5-FU), methotrexate (MTX), doxorubicin (DOX) or oxaliplatin (OXA). Drug-resistant invasive cells were compared to non invasive cells using cDNA microarray, qRT-PCR, flow cytometry, immunoblots and ELISA. Functional and cellular signaling analyses were undertaken using pharmacological inhibitors, function-blocking antibodies, and silencing by retrovirus-mediated RNA interference. 5-FU- and MTX-resistant HT-29 cells expressing an invasive phenotype in collagen type I and a metastatic behaviour in immunodeficient mice exhibited high expression of the chemokine receptor CXCR4. Macrophage migration inhibitory factor (MIF) was identified as the critical autocrine CXCR4 ligand promoting invasion in drug-resistant colon carcinoma HT-29 cells. Silencing of CXCR4 and impairing the MIF-CXCR4 signaling pathways by ISO-1, pAb FL-115, AMD-3100, mAb 12G5, and BIM-46187 abolished this aggressive phenotype. Induction of CXCR4 is associated with up-regulation of two genes encoding transcription factors previously shown to control CXCR4 expression (HIF-2a and ASCL2) and maintenance of intestinal stem cells (ASCL2). Enhanced CXCR4 expression was detected in liver metastases resected from colon cancer patients treated by the standard FOLFOX regimen. Combination therapies targeting the CXCR4-MIF axis can potentially counteract the emergence of the invasive metastatic behaviour in clonal derivatives of drug-resistant colon cancer cells.
2010-07-07 | GSE20147 | GEO
Project description:Although widely used in chemotherapy for colon cancer, 5-fluorouracil (5-FU) resistance is the main reason greatly limiting the efficacy of current therapies, leading to poor patient prognosis and survival. Histone lysine succinylation plays a vital role in various diseases by influencing gene expression and chromatin structure. However, limited information is currently available about the role of H3K23 succinylation associated with 5-FU resistance in colon cancer cells (CCCs). Here we explored the systematic alterations of H3K23s succinylation using the Cleavage Under Targets and Tagmentation (CUT&Tag), followed by integrated analysis of multi-omics data to identify potential regulators and their targets associated with differentially enriched regions (DERs) in the parental and 5-FU-resistant HCT15 colon cancer cells. More than 60,000 high-quality peaks were obtained from each sample with higher signal enriched at gene promoter regions. A total of 13,622 H3K23su DERs were identified in 5-FU-resistant HCT15 cells compared to control, which was positively (r = 0.68) correlated with their nearest differentially expressed genes (DEGs). The up-regulated DEGs associated with H3K23su GAIN regions are mainly involved in colorectal cancer, MAPK, Ras, and p53 signaling pathways, while the down-regulated DEGs related to H3K23su LOSS regions significantly enriched in the signaling pathways of Wnt and HIF-1. DNA motif analyses of the DER sequences showed that, besides AP-1, the members of FOX, GATA, and TEAD transcription factor (TF) families were potentially enriched in GAIN or LOSS regions with different preferences. Moreover, differentially expressed TFs and their potential targets associated with H3K23su DERs were identified, including FOSL21, FOXA1 and HNF1B, and known and predicted interactions among these critical TFs were further illustrated. These data provided clear insights and resources for an improved understanding of the role of H3K23su related to 5-FU resistance in colon cancer cells based on the multi-omics data, which allowed for the detection of epigenomic profiles, potential regulatory TFs, cis-regulatory elements, and therapeutic targets.
2023-06-20 | GSE234735 | GEO