These findings implicate miR-146a/b as a negative regulator of constitutive NF-kappaB activity in a breast cancer setting and suggest that modulating miR-146a/b levels has therapeutic potential to suppress breast cancer metastases.
These results further support the recent notion that modulating the levels of miR-146a or miR-146b could have a therapeutic potential to suppress breast cancer metastasis.
Recently, the SNPs rs11614913 in hsa-mir-196a2 and rs3746444 in hsa-mir-499 were reported to be associated with increased breast cancer risk, and the SNP rs2910164 in hsa-mir-146a was shown to have an effect on age of breast cancer diagnosis.
Several molecular epidemiological studies were conducted in recent years to evaluate the association between has-miR-146ars2910164 polymorphism and breast cancer risk in diverse populations.
These findings suggest that TRAIL-induced miR-146a expression suppresses CXCR4-mediated human breast cancer migration, and provide further insight into the non-apoptotic function of TRAIL in the prevention of metastasis as a therapy for breast cancer.
However, for the miR-146ars2910164 (G>C), miR-149 rs2292832 (G>T), miR-373 rs12983273 (C>T), and miR-423 rs6505162 (C>A) polymorphisms, we failed to find any significant association with the risk of breast cancer in any genetic model.
The rs11614913 (TT+CT) genotype of miR-196a2 was revealed to be associated with a decreased breast cancer susceptibility compared with the CC genotypes (OR = 0.906, 95% CI: 0.825-0.995, P = 0.039); however, no significant associations were observed between rs2910164 in miR-146a (or rs3746444 in miR-499) and breast cancer susceptibility.
Our study aimed to evaluate the possible association between four miRNA polymorphisms, hsa-miR-146a (rs2910164 G>C), hsa-miR-499 (rs3746444 T>C) and hsa-miRNA-196a2 (rs11614913 C>T and rs185070757 T>G), and susceptibility to breast cancer in an Iranian population.
BRCA1 regulation of epidermal growth factor receptor (EGFR) expression in human breast cancer cells involves microRNA-146a and is critical for its tumor suppressor function.
Meta-analyses showed that rs2910164 (miR-146a) was associated with BC risk in Caucasian population (homozygote comparison: OR = 1.29, 95%CI = 1.02-1.63, P=0.03; dominant model: OR = 1.31, 95% CI = 1.05-1.65, P=0.02), whereas negative results were obtained for Asians in all genetic models. rs11614913 (miR-196a2) was associated with BC risk in the overall population based on the recessive model (OR = 0.89, 95% CI = 0.80-0.99, P=0.03).
To determine the role of quercetin treated on breast cancer, we investigated the effect of quercetin on cell proliferation in human breast cancer cell lines MCF-7 and MDA-MB-231 with/without transfection of miR-146a mimic or anti-miR-146a.
Our results suggested that miR-146ars2910164 G>C and miR-196a2 rs11614913 T>C may be biomarkers for predicting breast cancer risk in the Chinese population.
Down-regulations of miR-146a and miR-146b expression in breast tissues were related to development and deterioration of breast cancer. miR-146a and miR-146b might act as potential biomarkers for young women with breast cancer.
The expression of microRNA‑146a (miR‑146a) has been reported to be significantly greater in patients with breast cancer compared with healthy controls.
The microRNA miR146a has a potential role in the development of breast cancer and the effects of its SNPs require further inquiry to determine the nature of their influence on breast tissue and cancer.
Association between three functional microRNA polymorphisms (miR-499 rs3746444, miR-196a rs11614913 and miR-146ars2910164) and breast cancer risk: a meta-analysis.