关键词: MicroRNA-21, 乳腺癌, 吉西他滨耐药, 上皮-间充质转化

Abstract:   Background and purpose: Gemcitabine-based chemotherapy has been shown to have significant activity and favourable safety in metastatic breast cancer patients, but the effectiveness is limited due to drug resistance. MicroRNAs are a family of small non-coding RNA molecules, acting as oncogenes or tumor suppressors. Although various mechanisms of chemoresistance have been uncovered, the aberrant microRNA expression and its relationship with drug resistance of breast cancer are still unclear. This study explored the potential role and underlying mechanism of microRNA-21 in gemcitabine resistant breast cancer. Methods: MDA-MB-231 cells were continuously exposed to the increasing concentrations of gemcitabine to induce drug resistance to gemcitabine, which was 10 times more resistant. Then multiple methods were used including real-time PCR (RT-PCR), CCK-8, Western blot, transfection, wound healing and Transwell assay to observe the effect of microRNA-21 on epithelial-mesenchymal transition (EMT) and chemosensitivity. Results: The expression of microRNA-21 was up-regulated in gemcitabine resistant breast cancer cell line and inversely correlated with gemcitabine sensitivity. Manipulation of microRNA-21 status could change microRNA- 21 level, and could result in corresponding changes in EMT status and drug sensitivity. Conclusion: MicroRNA-21 induces gemcitabine resistance possibly via EMT process in breast cancer.

Key words: MicroRNA-21, Breast cancer, Gemcitabine resistance, Epithelial to mesenchymal transition