Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-seq profiles between human parental and 5-FU drug resistant HCT116 and SW480 colorectal cancer cell lines

ABSTRACT: Colorectal cancer (CRC) is one of the most frequently diagnosed and lethal malignancy. Several key factors including poor dietary habits, smoking, alcohol consumption, genetic predisposition, obesity, diabetes mellitus, and sedentary lifestyle – all result in a significantly increased risk for developing CRC. Current treatment modalities for patients with CRC include surgery, which is often followed with adjuvant chemotherapy, especially in patients with a stage II and III disease. Most patients with advanced CRC are generally treated with the chemotherapeutic drug, 5-fluorouracil (5-FU) – either given alone or in combination with oxaliplatin and other molecularly-targeted drugs. While such treatment regimens are effective at improving disease outcomes, their clinical usefulness is often hampered due to the considerable toxicity associated with these treatments, which often causes severe nausea, vomiting, weight loss, and risk of infectious complications due to immunosuppression. Furthermore, their therapeutic efficacy is limited due to the emergence of chemotherapeutic drug resistance. In this study we performed genomewide transcriptomic analysis of parental and 5-FU resistant cells to identify differentially expressed genes and its associated pathways in promoting chemoresistance in CRC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE196900 | GEO | 2022/02/19

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

5- FU treated organoids

Project description:5-Fluorouracil (5-FU) is a chemotherapeutic drug component that is commonly used for the treatment of solid cancers. The anticancer properties of 5-FU have been attributed to interference with nucleotide synthesis and through direct incorporation into the DNA as being a pyrimidine analog. As both mechanisms of action may have a mutational impact on surviving tumor cells, we performed three independent analyses to characterize the genomic consequences of 5-FU treatment: i) in vitro treatment of intestinal organoids with 5-FU followed by whole genome sequencing, ii) genome-wide mutation analyses in tumor samples from 5-FU treated patients with breast or colorectal cancer, and iii) analysis of paired biopsies from patients treated with 5-FU between biopsies. Our results demonstrate that both in vitro and in vivo 5-FU causes a mutational pattern that is dominated by T>G substitutions in a CTT context and with strong resemblance to COSMIC signature 17. Interestingly, this signature is also found in non 5-FU treated patients, most prominently in esophageal tumors, indicating that distinct endogenous and exogenous triggers can converge into highly similar mutational signatures. Furthermore, our results suggest that 5-FU may have adverse mutagenic effects on healthy cells and contributes to genetic variability in surviving cancer cells thereby contributing to tumor evolution.

| EGAS00001003592 | EGA

Changes in mRNA Expression by schedule-dependent combination of 5-FU and selumetinib

Project description:Anti-tumor effect of the combination between 5-FU and selumetinib was treatment schedule-dependent in BRAF or KRAS mutant CRC cells. Treatment of 5-FU for 2 days followed by selumetinib for another 2 days exhibited synergism for cell viability, whereas single or reversely combined treatment showed antagonism Microarray analysis revealed the distinct groups of genes underlying the efficacy for schedule-dependent treatment.

2020-12-30 | GSE89531 | GEO

FU methane

Project description:FU methane Metagenome

| PRJNA756936 | ENA

Increased CD44 expression in low-dose chemotherapeutic treated colon cancer cells is controlled by ELF3

Project description:Background: It has been considered that long-term exposure to chemotherapeutic drugs would cause the development of resistance in colorectal cancer (CRC) patients. Though the detailed mechanism for this process is varied under different circumstances, the existence of cancer stem cells (CSCs) in CRC tissues has been proposed to be one of the reasons. Methods: In this study, low dose of fluorouracil (IC10 of 5-FU) treatment against colon cancer cells had been used to mimic the situation occurred in vivo when the cancer patients were received chemotherapy.

2022-01-21 | GSE193865 | GEO

p53 influences 5-FU-induced chromatin accessibility [ChIP-seq]

Project description:5-Fluorouracil (5-FU) is one of the most common drugs used in chemotherapy because of its efficacy and stability. However, 5-FU has been known to work on only 10~15% of colon cancer patients. Therefore, the study of 5-FU sensitivity study is necessary to increase the survival of colon cancer patients. p53 is one of the factors that effect on drug sensitivity. Main function of p53 has been focused on transcription activity in cell death. Numerous drug related studies show that expression of wild-type p53 increases drug sensitivity in various cancer types through inducing apoptotic signaling pathways. Currently, it has been reported that p53 has both transcriptional and non-transcriptional activities in apoptosis. However, most studies about p53 non-transcriptional activities in apoptosis are mainly focused on p53 induced mitochondrial outer membrane permeabilization, triggering the release of pro-apoptotic factors. The chromatin structure and organization have strongly attracted because of their impacts in cellular phenotypes. Recent studies have been shown that changes in chromatin accessibility affect cell phenotypes for external stimuli. Since p53 plays an important role in drug sensitivity and 5-FU is an external stimulus for cancer cells, we hypothesized that p53 may effect on 5-FU sensitivity through different regulation of chromatin accessible regions between TP53-WT and TP53-KO cells. To determine the effect of p53 on chromatin accessibility modification associated with 5-FU sensitivity, ATAC-seq and RNA-seq were performed under 5-FU treatment on TP53-WT as drug sensitive and TP53-KO as drug resistant HCT116 cells. In this study, we found that 5-FU induces chromatin accessibility in both TP53-WT and TP53-KO cells. Moreover, our results show that 5-FU induced chromatin accessibility increases expression of apoptotic genes in TP53-WT HCT116 cells through p53 non-transcriptional activity in nucleus.

2021-02-10 | GSE157950 | GEO

p53 influences 5-FU-induced chromatin accessibility [ATAC-seq]

2021-02-10 | GSE157949 | GEO

FU methane winter

Project description:FU methane winter Metagenome

| PRJNA797915 | ENA

The post-translational modifications and translation-regulatory role of METTL14 in 5-fluorouracil-resistant colorectal cancer [Ribo-seq]

Project description:5-fluorouracil (5‑FU) based chemotherapy is the first-line chemotherapy scheme for CRC, whereas acquired drug resistance poses a huge obstacle to curing CRC patients and the mechanism is still obscure. METTL14 is a core subunit of the m6A methyltransferase complex and has been reported to regulate the drug resistance of cancers. Here, we demonstrated that METTL14 is significantly downregulated in 5-FU-resistant CRC and METTL14 overexpression inhibits the proliferation and 5-FU resistance of CRC cells in vitro and in vivo. In addition, we found that MIB1 catalyzes the K63-linked ubiquitination of METTL14 and induces its degradation through the autolysosome pathway, while AURKA-mediated phosphorylation enhances METTL14 stability by inhibiting its ubiquitination. Moreover, we first discovered that METTL14 functions in 5-FU-resistant CRC cells by directly participating in the translation initiation of non-m6A-modified mRNAs independently of METTL3, rather than cooperating with METTL3 to methylate adenosine residues of targets. Further analysis indicated that METTL14 regulates the cell cycle process in 5-FU-resistant CRC cells. Collectively, our study not only identified METTL14 as a potential therapeutic target for 5-FU resistance in CRC but also revealed a novel translation-facilitating role of METTL14.

2023-12-01 | GSE219172 | GEO

The post-translational modifications and translation-regulatory role of METTL14 in 5-fluorouracil-resistant colorectal cancer [mRNA-seq]

2023-12-01 | GSE219171 | GEO

5-FU resistant ESCC

Project description:TE-5 and 5-FU resistant subline TE-5R

2015-06-03 | GSE69494 | GEO