Use of Gain-of-Function Screening to Identify miRNAs Involved in Paclitaxel Resistance in Triple-Negative Breast Cancer.

Paclitaxel is a widely used chemotherapeutic agent for the treatment of breast cancer (BC), including as a front-line treatment for triple-negative breast cancer (TNBC) patients. However, resistance to paclitaxel remains one of the major causes of death associated with treatment failure. Multiple studies have demonstrated that miRNAs play a role in paclitaxel resistance and are associated with both disease progression and metastasis. In the present study, we used a miRNA-encoding lentiviral library as a gain-of-function screen for paclitaxel resistance in the MDA-MB-231 TNBC cell line. We identified that , , , and conferred a resistant phenotype to cells. The expression of also induced resistance to eribulin and vinorelbine, while and induced resistance to vinorelbine. We measured the levels of these miRNAs in breast cancer patients and observed higher levels of in treatment-refractory patients. Taken together, we suggest that and may be good candidates for miRNA inhibition to overcome resistance to chemotherapy.