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