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:Folic acid is one of the B vitamins and is involved into neural function and brain development. Increasing evidence showed that folic acid can regulate neural gene function through DNA modification, while regulatory roles of folic acid in RNA modification remain largely unknown. In this study, we investigated the role of folic acid in regulating neural mRNA m6A epitranscriptome in Drosophila and mammals. We found that the folate treatment induced a significant increase in mRNA m6A levels compared to the control group in Drosophila and S2 cells. MeRIP-seq analysis indicated that carbon metabolism pathway and neural-related pathways were mainly affected. Subsequently, we migrated our validation experiments to human cells, our results showed that folate also affected mRNA m6A modification through one-carbon metabolic pathway in human cells, especially in neuronal cells. We also validated the effect of folic acid on mRNA methylation in mice, the results showed that folic acid treatment can significantly increase the expression of m6A-related proteins (Mettl3, Mettl14, FTO) and neural mRNA m6A methylation levels in mice brain. Moreover, we found that folic-acid producing Lactobacillus plantarum can significantly affects the m6A modification of mRNA in the host. In conclusion, we demonstrated that folic acid can participate in mRNA m6A modification through one-carbon metabolic pathway in Drosophila and mammals, and found that it has a significant effect on neural-related genes and pathways.
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