Omega-3 Polyunsaturated Fatty Acids Time-Dependently Reduce Cell Viability and Oncogenic MicroRNA-21 Expression in Estrogen Receptor-Positive Breast Cancer Cells (MCF-7)

Abstract

The omega-3 polyunsaturated fatty acid (n-3 PUFA), α-linolenic acid (ALA), and its metabolites, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), independently reduce the growth of breast cancer cells in vitro, but the mechanisms, which may involve microRNA (miRNA), are still unclear. The expression of the oncomiR, miR-21, is reduced by DHA treatment, but the effects of ALA on miR-21, alone or combined with EPA and DHA under physiologically relevant concentrations, have not been investigated. The effects of ALA alone and +/−EPA and DHA at the blood molar ratios seen in either humans (1.0:1.0:2.5, ALA:EPA:DHA) or mice (1.0:0.4:3.1, ALA:EPA:DHA) post flaxseed oil consumption (containing ALA) were assessed in vitro in MCF-7 breast cancer cells. Cell viability and the expression of miR-21 and its molecular target, phosphatase and tension homolog (PTEN, gene and protein), at different time points, were examined. At 1, 3, 48 and 96 h ALA alone and 24 h animal ratio treatments significantly reduced MCF-7 cell viability, while 1 and 3 h ALA alone and human and animal ratio treatments all significantly reduced miR-21 expression, and 24 h animal ratio treatment reduced miR-21 expression; these effects were not associated with changes in PTEN gene or protein expressions. We showed for the first time that ALA alone or combined with EPA and DHA at levels seen in human and animal blood post-ALA consumption can significantly reduce cell viability and modulate miR-21 expression in a time- and concentration-dependent manner, with the animal ratio containing higher DHA having a greater effect. The time dependency of miR-21 effects suggests the significance of considering time as a variable in miRNA studies, particularly of miR-21.

Cardioprotective Effects of Dietary Flaxseed Post-Infarction Are Associated with Changes in MicroRNA Expression

“…Flaxseed is the richest source of the plant-based omega-3 PUFA, ALA. Dietary supplementation with flaxseed has demonstrated anti-arrhythmic, antiatherogenic, antihypertensive, and cholesterol-lowering effects in animal and human studies [ 21 ]. Flaxseed and its components modulate the expression of miRNAs in breast cancer cells [ 30 , 31 ] and irradiated lung tissue [ 32 ]. However, no study has examined the effect of flaxseed or ALA on miRNAs in the setting of an MI.…”

microRNA Regulation in Estrogen Receptor-Positive Breast Cancer and Endocrine Therapy

“…In regards to the potential of miR-21 as a target for breast cancer inhibition, studies using cell models of ER + breast cancer have consistently reported that miR-21 inhibition suppresses ER + breast carcinogenesis [ 45 , 46 ]. Interestingly, several reports have indicated that non-pharmaceutical interventions can modulate miR-21 expression.…”

Identification of MiR-211-5p as a tumor suppressor by targeting ACSL4 in Hepatocellular Carcinoma

“…MicroRNAs (miRNAs), a class of non-coding RNAs with a length of 18 to 25 nucleotides, can regulate numerous cellular processes such as proliferation, apoptosis, cell cycle progression, differentiation, and DNA repair by suppressing translation of its target mRNA or by the promotion of mRNA degradation [ 7 , 8 ]. Furthermore, extensive research has found that over-expression or under-expression of a particular miRNA can regulate tumor cell proliferation, invasion and metastasis by modulating the expression of its target genes [ 9 – 11 ]. Therefore, identification of abnormally-expressed miRNAs and their downstream target genes in HCC enhance our understanding of the potential pathogenesis of HCC and represents a promising strategy for the diagnosis, treatment, and prognosis of HCC.…”