MicroRNA-125b Confers the Resistance of Breast Cancer Cells to Paclitaxel through Suppression of Pro-apoptotic Bcl-2 Antagonist Killer 1 (Bak1) Expression

摘要: Paclitaxel (Taxol) is an effective chemotherapeutic agent for treatment of cancer patients. Despite impressive initial clinical responses, the majority patients eventually develop some degree resistance to Taxol-based therapy. The mechanisms underlying cells Taxol are not fully understood. MicroRNA (miRNA) has emerged play important roles in tumorigenesis and drug resistance. However, interaction between development miRNA been previously explored. In this study we utilized a array compare differentially expressed miRNAs Taxol-resistant their Taxol-sensitive parental cells. We verified that miR-125b, miR-221, miR-222, miR-923 were up-regulated by real-time PCR. further investigated role miR-125b found was cells, causing marked inhibition Taxol-induced cytotoxicity apoptosis subsequent increase Moreover, demonstrated pro-apoptotic Bcl-2 antagonist killer 1 (Bak1) direct target miR-125b. Down-regulation Bak1 suppressed led increased Taxol. Restoring expression either inhibitor or re-expression miR-125b-overexpressing recovered sensitivity, overcoming miR-125-mediated Taken together, our data strongly support central conferring through suppression expression. This finding implications targeted therapeutics number different tumor histologies.