Association between three functional microRNA polymorphisms (miR-499 rs3746444, miR-196a rs11614913 and miR-146ars2910164) and breast cancer risk: a meta-analysis.
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.
Double luciferase reporter gene was used to verify the target regulatory relationship between miR-146 and NM23-H1 on a human breast cancer cell line. miR-146a was closely related to the proliferation and metastasis of breast cancer. miR-146a also promoted the growth of breast cancer in vivo via targeting NM23-H1.
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.
Epigenetic origin of the link between obesity and breast cancer (BC) is investigated in a cohort of Tunisian patients, focusing on polymorphism at germline level (miR-146a) and on expression in mammary tumors (miR-21, miR-146a, and miR-34a), according to body mass index (BMI) and clinico-pathologic features.
Here, we show that the histone deacetylase inhibitor, trichostatin A (TSA), suppresses HER2-overexpressing breast cancer via upregulation of miR-146a and the resultant repression of its oncogenic targets, interleukin-1 receptor-associated kinase 1 and the chemokine receptor CXCR4.
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.
In addition, miR-15/107/182-mediated downregulation of BRCA1 interrupt DNA repair and may change the course of BC therapy. miR-146a and miR-146-5p silencing BRCA1 may trigger formation of triple-negative and basal-like sporadic BC cases. miR-182 might effect the therapy outcome. miR-21 targeted therapy might be useful for the treatment of BRCA2 mutation carriers. miR-342 overexpression and the absence of functional BRCA1 gene might cause synthetic lethality, which might be used as a base for future therapies.
It was concluded that miR-146a-5p is expressed in breast cancer tissue and breast cancer cell line and may regulate the proliferation of MCF-7 via BRCA1.
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).
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.
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.
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.
Results The CC homozygous genotype of miR-146a (rs2910164) was seen in 45(12.7%) patients with breast cancer and 18(5.1%) controls (OR 4.09 [95%CI 2.19-7.67] p < 0.001).
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.