Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA130627 | ENA |
REPOSITORIES: ENA
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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:In the present study, we investigated miRNA expression changes caused by aquired chemoresistance to 5-FU or Oxa. 40 and 14 miRNAs were detected as differentially expressed in 5-fluouracil- and oxaliplatin-resistant colorectal HCT116 sublines, respectively. Differentially expressed miRNAs determined in the present study could be applied for further development of diagnostic and therapeutic applications for colorectal cancer carcinoma resistant to 5-FU or Oxa.
2019-12-31 | GSE119481 | GEO
Project description:We observed human colorectal cancer cell lines obtained resistance under treatment, and resistant cells switched back to sensitive state when the treatment is withdrawn. To understand gene expressions change during this process, we performed Affymetrix experiments for parental, R20 (resistant), and W20 (withdrawal treatment) clones for three colorectal cancer cell lines.
2024-04-03 | GSE255674 | GEO
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:In Alternative Expression Analysis (ALEXA)-Seq we developed a method to analyze massively parallel RNA sequence data to catalogue transcripts and assess differential and alternative expression of known and predicted messenger RNA (mRNA) isoforms in cells and tissues. As proof-of-principle, we applied the approach to a comparison of fluorouracil responsive and non-responsive human colorectal cancer cell lines. The sensitivity and specificity of the approach were assessed by comparison to exon tiling and splicing microarrays. Validations were conducted by reverse transcription polymerase chain reaction (PCR), quantitative PCR and Sanger sequencing. We observed global disruption of splicing in resistant cells characterized by expression of novel mRNA isoforms resulting from exon skipping, alternative splice site usage and intron retention. Alternative expression annotation databases, source code, a data viewer and other resources to facilitate analysis are available at our website: www.AlexaPlatform.org. See Griffith et al. 2010 in Nature Methods for further details.
2010-08-25 | GSE23776 | GEO
Project description:microRNA and mRNA profiling was conducted for parental cell lines and cell lines resistant to trifluridine in 3 colorectal cell lines (DLD-1, HCT-116, RKO). We hypothesized that a detailed comparison between miRNA and mRNA expression might reveal the mechanism for acquired resistant to trifluridine in colorectal cancer.
2017-09-25 | GSE96786 | GEO
Project description:microRNA and mRNA profiling was conducted for parental cell lines and cell lines resistant to trifluridine in 3 colorectal cell lines (DLD-1, HCT-116, RKO). We hypothesized that a detailed comparison between miRNA and mRNA expression might reveal the mechanism for acquired resistant to trifluridine in colorectal cancer.
2017-09-25 | GSE96785 | GEO
Project description:Copy number profiling of MKN45T 5-FU resistant gastric cancer cell lines and its parental cell line MKN45. We hypothesized that a detailed fine-scale survey of genomic CNAs might reveal the mechanism for acquired resistant to 5-FU in gastric cancer.
2017-06-09 | GSE89191 | GEO
Project description:5-Fluorouracil (5-FU) is a widely used chemotherapeutic drug in colorectal cancer. Previous studies showed that 5-FU modulates RNA metabolism and mRNA expression. In addition, it has been reported that 5-FU incorporates into the RNAs constituting the translational machinery and that 5-FU affects the amount of some mRNAs associated with ribosomes. However, the impact of 5-FU on translational regulation remains unclear. Using translatome profiling, we report that a clinically relevant dose of 5-FU induces a translational reprogramming in colorectal cancer cell lines. Comparison of mRNA distribution between polysomal and non-polysomal fractions in response to 5-FU treatment using microarray quantification identified 313 genes whose translation was selectively regulated. These regulations were mostly stimulatory (91%). Among these genes, we showed that 5-FU increases the mRNA translation of HIVEP2, which encodes a transcription factor whose translation in normal condition is known to be inhibited by mir-155. In response to 5-FU, the expression of mir-155 decreases thus stimulating the translation of HIVEP2 mRNA. Interestingly, the 5-FU-induced increase in specific mRNA translation was associated with reduction of global protein synthesis. Altogether, these findings indicate that 5-FU promotes a translational reprogramming leading to the increased translation of a subset of mRNAs that involves at least for some of them, miRNA-dependent mechanisms. This study supports a still poorly evaluated role of translational control in drug response.
2017-05-23 | GSE77180 | 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