WITHDRAWN: Genetic polymorphisms and promoter methylation of miR-9-3 in the modulation of breast cancer risk in a Chinese population

Abstract

<h2>Abstract</h2><h3>Background</h3> <b>:</b> Genome-wide association study has discovered some susceptibility loci of breast cancer (BC), such as 1q32.1, 5q14.3, and 15q26.1. miR-9-3, located on 15q26.1, was down-regulated in BC, involving in estrogen receptor-α signaling pathway and p53-related apoptotic pathway. We aimed to investigate the role of genetic polymorphisms and promoter methylation of miR-9-3 in the modulation of BC risk. <h3>Materials and Methods</h3> <b>:</b> The rs4335754 and rs4932217 in the promoter of miR-9-3 were genotyped using the Taqman assay. The relative expression levels of miR-9-3 and <i>CDH1</i> were measured by qRT-PCR. miR-9-3 promoter methylation was examined by bisulfate genomic sequencing and transcriptional activity was evaluated by dual-luciferase reporter assay. <h3>Results</h3> <b>:</b> The rs4335754 GG, AG/GG genotypes, and G allele were associated with a reduced risk of BC (GG vs. AA: adjusted OR = 0.46, 95 % CI, 0.26-0.79, <i>p</i> = 0.004; AG/GG vs. AA: adjusted OR = 0.72, 95 % CI, 0.56-0.92, <i>p</i> = 0.009; G vs. A: adjusted OR = 0.73, 95 % CI, 0.60-0.89, <i>p</i> = 0.002, respectively). The rs4335754 AG/GG carriers displayed high levels of miR-9-3 and the rs4335754 G allele increased promoter activity. Moreover, miR-9-3 promoter hypermethylation can also reduce the expression of miR-9-3. Ectopic expression of miR-9-3 inhibited cell proliferation through targeting <i>CDH1.</i> <h3>Conclusion</h3> <b>:</b> These findings indicate that rs4335754 as well as CpGs methylation in the promoter of miR-9-3 altered its expression, and ultimately affected individual's susceptibility for the development of BC.