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 miR-181b, miR-29a, miR-30c, miR-196 and miR-1295 conferred a resistant phenotype to cells. The expression of miR-29a also induced resistance to eribulin and vinorelbine, while miR-181b and miR-30c induced resistance to vinorelbine. We measured the levels of these miRNAs in breast cancer patients and observed higher levels of miR-29a in treatment-refractory patients. Taken together, we suggest that miR-29a and miR-181b may be good candidates for miRNA inhibition to overcome resistance to chemotherapy.