miR-181a表达水平与ER阳性乳腺癌对内分泌治疗敏感性的关系

目的:研究miR-181a表达水平与雌激素受体（estrogen receptor,ER）阳性乳腺癌对内分泌治疗敏感性之间的关系。方法:采用梯度递增法诱导乳腺癌他莫昔芬耐药细胞株，利用集落形成实验检测细胞对他莫昔芬的敏感性。利用RT-PCR法检测miR-181a表达的情况，利用KM-plotter分析miR-181表达与乳腺癌患者预后之间的关系。结果:我们成功的诱导了MCF-7他莫昔芬继发耐药细胞株TAM-R。RT-PCR分析结果显示:他莫昔芬继发耐药的TAM-R细胞株及原发他莫昔芬耐药BT474细胞株中miR-181a的表达水平均显著高于对他莫昔芬敏感的MCF-7细胞株。生存分析结果显示:miR-181a的表达水平与ER阴性乳腺癌患者的总生存无关，但在ER阳性乳腺癌中miR-181a表达高的患者总生存明显差于miR-181a低表达者。进一步分析结果显示:在ER阳性但未接受内分泌治疗的乳腺癌患者中miR-181a表达与总生存无关，但在ER阳性且接受过内分泌治疗的乳腺癌患者中miR-181a高表达者总生存显著差于miR-181a低表达者。结论:miR-181a高表达ER阳性乳腺癌患者对内分泌治疗敏感性差，miR-181a可能是预测ER 阳性乳腺癌对内分泌治疗敏感性的指标。

To explore the relationship between miR-181a and endocrine therapy efficiency of ER positive breast cancer

Objective:To investigate the expression of miR-181a and endocrine-therapy sensitivity of estrogen receptor (ER) positive breast cancer.Methods:We constructed tamoxifen-resistant MCF-7 cell line using gradient incremental method.Cells proliferation was measured using colony formation assay.The expression of miR-181a was determined by RT-PCR.The prognostic value of miR-181a in breast cancer was analyzed using Kaplan-Meier Plotter.Results:We successfully constructed a cell line resistant to tamoxifen (TAM-R).RT-PCR results showed that the expression of miR-181a was higher in tamoxifen induced and primary resistance cell lines than tamoxifen sensitive cell line.High expression of miR-181a predicted significantly poorer overall survival (OS) in ER-positive but not ER-negative breast cancer.Further analysis showed that high expression of miR-181a was associated with poorer OS in endocrine-therapy treated ER-positive breast cancer but not in ER-positive breast cancer without endocrine-therapy treatment.Conclusion:High expression of miR-181a predicted less sensitive to endocrine therapy in ER positive breast cancer.miR-181a might be a promising predictor of the efficacy of endocrine therapy.