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MiRNA profiling data of mouse bone marrow samples four days post 5-FU treatment versus untreated controls

ABSTRACT: To identify miRNAs that regulate hematopoietic response after 5-FU-induced injury, we analyzed miRNA expression changes in bone marrow cells from mice with or without 5-FU treatment. Global miRNA expression profiling of the 5-FU and untreated cohorts showed that 92 miRNAs (among 168 that passed the detection threshold) were significantly upregulated or downregulated, with false discovery rates < 5%.

ORGANISM(S): Mus musculus

PROVIDER: GSE39211 | GEO | 2012/09/24

SECONDARY ACCESSION(S): PRJNA170232

REPOSITORIES: GEO

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miRNA profiling data of mouse bone marrow samples four days post 5-FU treatment versus untreated controls

Project description:To identify miRNAs that regulate hematopoietic response after 5-FU-induced injury, we analyzed miRNA expression changes in bone marrow cells from mice with or without 5-FU treatment. Global miRNA expression profiling of the 5-FU and untreated cohorts showed that 92 miRNAs (among 168 that passed the detection threshold) were significantly upregulated or downregulated, with false discovery rates < 5%. Female 6wk-old C57Bl6/J mice were left untreated or given a single dose of 5-FU (150mg/kg). Four days post treatment whole bone marrow was isolated from each animal (n=3 for treated and n=5 for untreated controls) and lysed for total RNA using Trizol (Invitrogen). Samples were profiled for miRNA expression using a bead-based profiling methodology (Lu et al., 2008). Profiling data were normalized assuming equal total miRNA expression across samples. Differential miRNA expression was analyzed by studentM-bM-^@M-^Ys t-test and then calculated for false discovery rate using the Benjamini and Hochberg method.

2012-09-24 | E-GEOD-39211 | biostudies-arrayexpress

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Project description:Purpose: The goals of this study are to elucidate the underlying mechanism for the regulation of HSC divisions. Methods: Before or after wild type (WT) mice were treated with 5-fluorouracil (5-FU), 12500 cells of HSCs were sorted. These cells were subjected to CUT&Tag-seq to analyze H3K27ac profile by using Next-seq. The sequence reads that passed quality filters were analyzed by Trimmomatic.

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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.

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