The Preliminary Exploration Of The Role Of MiRNA In Breast

Objective To identify miRNA associated with breast cancer formation and progress, especially, the miRNA associated with the efficiency the chemotherapy. Establish a method for breast cancer prognosis by miRNA.Methods Afterwards, we use Qrt-PCR to measure miRNA expression levels in breast cancer and breast hyperplasia including miR-125α、miR-145、miR-155、miR-203、 miR-210and let-7a and analyze that if miRNA expression level measured above correlates with tumor size, metastasis and the expression of biomarkers measured above. Finally, we compare miRNAs expression levels changes in breast cancer cell lines treated with or without doxorubicin, cisplatin and paclitaxel, respectively.Results Our experimental results show that miR-145in tumor tissue was significantly down-regulated, while miR-155in tumor tissue was significantly up-regulated. Both miR-125a and let-7a positively correlate with patient’s age. Meanwhile let-7a negatively correlates with tumor size. miR-155, miR-203and miR-210expression in stage Ⅰ and Ⅱ tumors were lower than that in stage Ⅲ tumor samples. Unexpectedly, miR-203expression level in stage Ⅲ tumor is higher than that in stage Ⅱ breast cancer. Limited by sample amount, we found none of six miRNA significantly correlated with the expression status of biological markers in our study. miRNA expression level in tumor were compared before and after chemotherapy and we found expression of miR-145increased, while miR-210decreased after chemotherapy. At last, the MCF-7and Bcap37cell lines were treated with or without doxorubicin, cisplatin and paclitaxel, respectively. miR-125a significantly increased in MCF-7cells after treatment with three chemotherapy drugs. Doxorubicin and cisplatin also up-regulated miR-145in MCF-7cells. Doxorubicin treatment in Bcap37cells resulted in significant up-regulation in all of miRNA except let-7. Cisplatin led to miR-210up-regulation in Bcap37cells. Paclitaxel led to reduced expression of miR-125and miR-145, while increased expression of miR-203. In MDA-MB-468, doxorubicin treatmentlead miR-203down-regulate smoothly, cisplatin treatment lead increase of miR-203and decrease of let-7a, both miR-125a and miR-203were decreasing in paclitaxel withmiR-155increased; In MDA-MB-231cells, doxorubicin induce increase of miR-145, miR-203and let-7a, cisplatin induce increase of miR-145, miR-155and miR-203; In HCC1937cell lines, doxorubicin induce decrease of miR-125a, miR-145, miR-203and let-7a, cisplatin induce decrease of miR-125a and miR-155with increase of miR-203, paclitaxel induce decrease of miR-125a、miR-145and miR-203.Conclusion In summary, the expression of miR-145and miR-155can be served as indicators of cancer diagnosis. Patients with increase of the expression of miR-145or decrease of the expression of miR-155indicates that there is a risk of cancer. High expression levels of miR-155and miR-210may indicate whether the tumor progressed to stage Ⅲ or IV. The expression levels of miR-145significantly increased and the expression level of miR-210significant decreased after FEC regimen treatment in clinically, suggesting that these changes are likely related to the effect of chemotherapy.