MiRNA-206Was Associated With The Development And Progress Of Breast Cancer

Background and PurposeTremendous researches had showed that microRNA was correlated with the regulation of breast cancer. What’s more, some researchers had hypothesized that estrogen receptor be a target gene of miR-206. Therefore, the latter might have an important role in the development and progress of breast cancer. The purpose of this research was to investigate the relationship between miR-206and breast cancer and find the possible reasons for the development of the disease.Methods1) We extract the RNA and test the expression level of miR-206in HBL100, MCF-7and MDA-MB-203cell respectively.2) We used mimic, inhibitor and their negative controls to test the correlation between different expression level of miR-206and the proliferation, invasion and apoptosis of MCF-7and MDA-MB-203breast cancer cells.3) We used710breast cancer cases and294cancer free controls in the Department of Breast Surgery at Shanghai Cancer Hospital of Fudan University.4) We extracted the DNA and tested the polymorphisms of the SNPs in the binding area of miR-206and some of its target genes. SNP genotyping was used MassARRAY system (Sequenom) by means of matrix assisted laser desorption ionisation-time of flight mass spectrometry method (MALDI-TOF) according to the manufacturers instructions.5) We evaluated the odds ratios (OR) and their95%confident intervals (95%CI) of the associations between the SNPs’polymorphism in the binding area of miR-206and some of its target genes and breast cancer risk.Result1) Our tests showed that the expression level of miR-206in breast cancer cells were higher than epithelial cell of mammary gland whereas the expression level of miR-206in MDA-MB-231cell was higher than MCF-7cell.2) We also found that increasing the expression level of miR-206in MCF-7breast cancer cell would inhibit proliferation, invasion and promote apoptosis while decreasing the expression level of miR-206in the same cell would not impact proliferation, invasion and apoptosis. Moreover, increasing or decreasing the expression level of miR-206in MDA-MB-231breast cancer cell would not change the proliferation, invasion and apoptosis significantly.3) Our analysis had demonstrated for SNP rs3802278, located in the binding area between miR-206and SULF1, there was a trend of a decreased breast cancer risk (OR=0.834, P=0.081) compared AA genotype to GG genotype. Also, recessive model had less breast cancer risk (OR=0.663, P=0.032). For ER positive breast cancer, there was a lower breast cancer risk for AA genotype and recessive model (OR=0.800, P=0.046and OR=0.620, P=0.021respectively). For HR positive breast cancer, GA genotype and recessive model had a decreased breast cancer risk (OR=1.698, P=0.000).4) For SNP rs1224873, located in the binding area between miR-206and PDCD4, there was a trend of a lower breast cancer risk for GA genotype and recessive model (OR=0.763, P=0.072and OR=0.782, P=0.085respectively). For HR positive breast cancer, both GA and AA genotype had a higher breast cancer risk compared to GG genotype (OR=1.295,P=0.045and OR=1.645, P=0.001respectively).5) For SNP rs1044268, located in the binding area between miR-206and NRP1, AG genotype compared to AA genotype had a higher breast cancer risk in HR positive breast cancer (OR=1.973, P=0.000).6) For SNP rs14138, located in the binding area between miR-206and PRKCE, AA genotype compared to GG genotype had a significant higher breast cancer risk in HR positive breast cancer(OR=8.398, P=0.000).7) For SNP rs66916453, located in the binding area between miR-206and RICTOR and SNP rs881, located in the binding area between miR-206and TACR1, there were no significant differences among all the genotypes. ConclusionOur study showed that the expression level of miR-206might have an important impact on the biological behavior of breast cancer cell, especially the ER positive breast cancer cell. Therefore, miR-206might play an essential role in the development and progress of breast cancer. In addition, the polymorphism of of the SNPs in the binding area of miR-206and some of its target genes might have a strong relationship with breast cancer risk.