Relationship Between The Single Nucleotide Polymorphisms In Has-mir-125a-5p Rs12975333 And Expression Of Has-mir-125a-5p In Breast Cancer

Background: MicroRNAs (miRNAs) is an endogenous single chain non-coding RNA of 18-25 nt. MiRNA's initial transcript (pri-miRNA) in the nucleus is converted into approximately 70-90 nt hairpin precursors (pre-miRNA), then transported out of nucleus, and processed by Dicer enzyme to mature miRNA . The primary function of mature miRNA is to posttranscriptionally repressesgene expression. Recently, miRNAs have been shown to act as tumor suppressors or facilitators. Breast cancer is a multiple gene disease with a high incidence. Genetic susceptibility and interaction between genes and environment also play an important role in the pathogenesis of breast cancer. MiR-125a is located at chromosome 19 q13.43, which contains 2 miRNAs (miR125a-5p and miR125a-3p).has-mir-125a-5p has been shown to paly a role in growth, differentiation, and metastases of tumor cells. A previous study shows single nucleotide polymorphism(SNP) of rs12975333 locus in has-mir-125a-5p gene is correlated with the pathogenesis of breast cancer. To the best of our knowledge, the association of has-mir-125a-5p polymorphisms with breast cancer risk has not been studied in the Chinese population.Objective:To investigate the relationship between the SNPs in has-mir-125a-5p rs12975333 and the expression of has-mir-125a-5p and clinicopathological heracteristics of female breast cancer in shandong Chinese.Methods:Genomic DNA was extracted from peripheral blood lymphocytes. Taqman-MGB assay used to type breast cancer of 338 cases and 338 controls. Then the expression levels of has-mir-125a-5p in 289 biopsies were examined using stem-loop realtime RT-PCR and the clinicopathological cheracteristics of breast cancer and evaluate whether differentttttially expression of has-mir-125a-5p in various biopathologic features associated with tumor specimens.Result:The gene frequencies (GG,GT,TT)of rs12975333 in the patients were GG 273 (94.5%),GT 16 (5.5%),TT 0 (0%).In Breast fibroadenoma and controls were GG 49 (100%),338 (100%). Moreover,the expression level of has-mir-125a-5p in breast cancer (0.19±0.04)was obviously lower than that in the matched nontunor adjacent tissue specimens (0.37±0.05)(P =0.04)。The expression level of Minor T allele of mature has-mir-125a-5p in breast cancer(0.29±0.04)was obviously lower than that has-mir-125a-5p-GG carying(P =0.022).The expression of has-mir-125a-5p is down-regulated in primary breast ca ncer,especially in patients with women Later age of onset (P =0.036) and different lymph node metastasis groups (P = 0.001) and ERBB2 (P =0.007),ERBB3(P =0.04) negatively.Conclusion:rs12975333 polymorphisms in has-mir-125a-5p gene may contribute to the risk of breast cancer in hanzu shandong Chinese population.The altered expression of has-mir-125a-5p might play arole in the pathogenesis and progression of breast carcinoma,and it may be a useful moleeular marker for breast carcinoma.