Project description:Folic acid is involved in DNA methylation, thereby it can potentially induce gene silencing. We used microarrays to detect the transcripts that are showing different expressions after short-term folic acid (FA) treatment.
Project description:The effect of folic acid (FA) on breast cancer (BC) risk is uncertain. We hypothesised that this uncertainty may be due, in part, to differential effects of FA between BC cells with different phenotype. To test this we investigated the effect of treatment with FA concentrations within the range of unmetabolised FA reported in humans on the expression of the transcriptomes of non-transformed (MCF10a) and cancerous (MCF7 and Hs578T) BC cells. Total RNA obtained from three breast cancer cell lines (MCF10a, MCF7, Hs578T) treated with 100nmoles/l folic acid untreated control cells. Six replicates per treatment group.
Project description:We have previously shown that withdrawal of folic acid led to metabolic reprogramming and a less aggressive phenotype in a cell model of triple-negative breast cancer (TNBC). Herein, we evaluate the effects of folic acid withdrawal on transcriptomic profiles in these cells. Murine cell lines were originally derived from a pool of spontaneous mammary tumors grown in MMTV-Wnt1 transgenic mice. Based on their differential molecular characteristics and metastatic potential, these cell lines were previously characterized as non-metastatic epithelial (E-Wnt), non-metastatic mesenchymal (M-Wnt) and metastatic mesenchymal (metM-Wntliver) cells.
Project description:Folic acid is present in pre-natal vitamins, fortified cereal grains and multi-vitamin supplements. High intake of folic acid through these sources has resulted in populations with increased levels of serum folate and unmetabolized folic acid. Although the benefits of folic acid in the prevention of neural tube defects are undeniable, the impact of long-term consumption of folic acid on the prostate is not fully understood. In this study, we used a rodent model to test whether dietary folic acid (FA) supplementation changes prostate homeostasis and response to androgen deprivation. Although intact prostate weights do not differ between diet groups, we made the surprising observation that dietary folic acid supplementation confers partial resistance to castration-mediated prostate involution. More specifically, male mice that were fed a folic acid supplemented diet and then castrated had greater prostate wet weights, greater prostatic luminal epithelial cell heights, and more abundant RNAs encoding prostate secretory proteins compared to mice that were fed a control diet and castrated. We used RNA-seq to identify signaling pathways enriched in the castrated prostates from folic acid supplemented diet fed mice compared to control mice. We observed differential expression of genes involved in several metabolic pathways in the FA supplemented mice. Together, our results show that dietary FA supplementation can impact metabolism in the prostate and attenuate the prostate’s response to androgen deprivation. This has important implications for androgen deprivation therapies used in the treatment of prostate disease, as consumption of high levels of folic acid could reduce the efficacy of these treatments.
Project description:We report that fortified levels of folic acid adversely affect cilia strucure and function. This data set agrees with previous experiements which have demonstrated that elevated folic acid levels can increase transcription variability on a genome-wide level. Furthermore, we demonstrate that among these dysregulated genes, genes contained within SYSgold cilia database are proportionally over-represented. This over-representation of cilia genes among dysregulated genes may play a key role in ciliopathys' sensitivity to elevated folic acid levels.
Project description:DNA methylation profiles from saliva collected from 89 mothers and 179 adolescent children who received or did not receive perinatal folic acid supplementation Periconceptional folic acid supplementation and DNA methylation patterns in adolescents
Project description:Folic acid supplementation (8 mg/kg diet) promotes colon tumor formation in mice with established colitis induced by carcinogen azoxymethane (AOM) and dextran sulfate sodium sulfate (DSS). This induction of colon tumors was associated with hypomethylation of DNA cased by folic acid supplementation.