Folic acid modulates cancer‐associated micro RNAs and inflammatory mediators in neoplastic and non‐neoplastic colonic cells in a different way

Niemann, Birgit; Nemitz, Anke; Werner, Josephine; Dong, Ha Thanh; Steinberg, Pablo; Lampen, Alfonso; Ehlers, Anke

doi:10.1002/mnfr.201700260

Cited by 4 publications

(3 citation statements)

References 49 publications

(71 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…High-dose folic acid supplementation or high circulating levels of folic acid in healthy young individuals as well as in obese post-menopausal women were associated with reduced numbers and cytotoxicity of natural killer cells and altered expression profiles of cytokines [68,69]. Exposure of human colonic cell lines to increasing doses of folic acid resulted in altered expression of inflammatory mediators, with effects differing for nonmalignant and malignant cell lines [70]. The relationship between high folic acid intake and reduced natural killer cell cytotoxicity was also confirmed in murine studies and was, at least partially, attributed to reduced interleukin (IL)-10 production with excess folic acid [71].…”

Section: Discussionmentioning

confidence: 99%

Effects of folic acid withdrawal on transcriptomic profiles in murine triple-negative breast cancer cell lines

et al. 2020

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of folic acid withdrawal on transcriptomic profiles in murine triple-negative breast cancer cell lines

et al. 2020

View full text Add to dashboard Cite

show abstract

“…While high-physiological FA concentration had no influence on promoter methylation, in the HT29 cell line, tumor-suppressive micro RNAs were predominantly downregulated and the expression of genes involved in chemotaxis and immunity was modulated. In non-malignant HCEC cells folic acid didn’t affect pro-inflammatory genes and cancer-associated microRNA expression [ 166 ]. Some studies demonstrated that DNA methylation may be considered as a biomarker of colorectal cancer and that methylation of DNA in the colonic tissues and leukocytes can be increased by supplementation with folic acid [ 143 , 167 , 168 ].…”

Section: Problem Of Folate Deficiency and Oversupplementationmentioning

confidence: 99%

The Concept of Folic Acid in Health and Disease

et al. 2021

View full text Add to dashboard Cite

Folates have a pterine core structure and high metabolic activity due to their ability to accept electrons and react with O-, S-, N-, C-bounds. Folates play a role as cofactors in essential one-carbon pathways donating methyl-groups to choline phospholipids, creatine, epinephrine, DNA. Compounds similar to folates are ubiquitous and have been found in different animals, plants, and microorganisms. Folates enter the body from the diet and are also synthesized by intestinal bacteria with consequent adsorption from the colon. Three types of folate and antifolate cellular transporters have been found, differing in tissue localization, substrate affinity, type of transferring, and optimal pH for function. Laboratory criteria of folate deficiency are accepted by WHO. Severe folate deficiencies, manifesting in early life, are seen in hereditary folate malabsorption and cerebral folate deficiency. Acquired folate deficiency is quite common and is associated with poor diet and malabsorption, alcohol consumption, obesity, and kidney failure. Given the observational data that folates have a protective effect against neural tube defects, ischemic events, and cancer, food folic acid fortification was introduced in many countries. However, high physiological folate concentrations and folate overload may increase the risk of impaired brain development in embryogenesis and possess a growth advantage for precancerous altered cells.

show abstract

“…FA plays a critical role in de novo synthesis of nucleic acid synthesis and biological methylation [ 5 ], and it is related to maintaining the health of the human genome. FA deficiency is therefore hypothesized to contribute to CRC through disruption of these processes [ 6 , 7 ], and moderate amounts of FA can protect the normal colorectal mucosa [ 8 , 9 ]. Inversely, the excessive intake of FA may accelerate the progression of precancerous tissues to malignancy [ 10 – 12 ].…”

Section: Introductionmentioning

confidence: 99%

miRNA-mRNA Regulatory Network Reveals miRNAs in HCT116 in Response to Folic Acid Deficiency via Regulating Vital Genes of Endoplasmic Reticulum Stress Pathway

Lü

Zhao

et al. 2021

BioMed Research International

View full text Add to dashboard Cite

Moderate folic acid (FA) intake is an effective strategy that slows colorectal cancer (CRC) progression. However, high consumption of FA may trigger the transition of precancerous tissue towards malignancy. MicroRNAs (miRNAs) are considered to be potential biomarkers of CRC. Thus, identification of miRNAs of dysregulated genes in CRC cells by detailed analysis of mRNA and miRNA expression profile in the context of FA deficiency could substantially increase our understanding of its oncogenesis. mRNA-seq and miRNA-seq analyses were utilized to investigate the expression of miRNAs in FA-deficient CRC cell line–HCT116 through massive parallel sequencing technology. A total of 38 mRNAs and 168 miRNAs were identified to be differentially expressed between CRC groups with or without FA deficiency. We constructed an miRNA-mRNA network for the vital regulatory miRNAs altered in FA-deficient CRC cells. The mRNAs and miRNAs validated by Western blotting and RT-qPCR were consistent with the sequencing results. Results showed that FA deficiency upregulated some miRNAs thereby inhibiting the expression of critical genes in the endoplasmic reticulum (ER) stress pathway. Dysregulated miRNAs in our miRNA-mRNA network could contribute to CRC cell in response to deficient FA. This work reveals novel molecular targets that are likely to provide therapeutic interventions for CRC.

show abstract

Folic acid modulates cancer‐associated micro RNAs and inflammatory mediators in neoplastic and non‐neoplastic colonic cells in a different way

Abstract: The different effects of high-physiological FA concentrations in malignant and non-malignant colonic cell lines regarding cancer-associated miRNAs and inflammatory mediators may contribute to the different effects of FA supplementation on colonic carcinogenesis.

Cited by 4 publications

References 49 publications

Effects of folic acid withdrawal on transcriptomic profiles in murine triple-negative breast cancer cell lines

Effects of folic acid withdrawal on transcriptomic profiles in murine triple-negative breast cancer cell lines

The Concept of Folic Acid in Health and Disease

miRNA-mRNA Regulatory Network Reveals miRNAs in HCT116 in Response to Folic Acid Deficiency via Regulating Vital Genes of Endoplasmic Reticulum Stress Pathway

Contact Info

Product

Resources

About