Acquired resistance to classical chemotherapeutics such as docetaxel (DTX) remains a critical challenge in breast cancer (BCa) treatment. Epigenetic modification by microRNAs (miRNAs) has been shown to play a crucial role in cancer drug resistance. Previous study, using human drug-resistant BCa tissues, has identified miR-638 as one of the most down-regulated miRNAs, but its exact roles and underlying mechanisms during the pathogenesis of chemoresistance remain to be determined. In the current study, we found that miR-638 expression was significantly down-regulated in clinical DTX-resistant BCa tissues compared to that in DTX-sensitive BCa tissues. By using the previously established DTX-resistant MCF-7 cells (MCF-7/R), we also confirmed that chemoresistant cells displayed decreased levels of miR-638. To provide the direct functional evidence, we inhibited and overexpressed miR-638 in different cell lines. Thereby, the cells were rendered more resistant or susceptible to DTX treatment. Mechanistically, the lipid-binding protein STARD10 was identified as a miR-638 target mediating the DTX-resistance. Hence, we provide a molecular explanation for acquired resistance to DTX that is caused by the miR-638 deficiency and subsequent STARD10 upregulation. In consequence, alteration of miR-638/STARD10 cascade may represent an attractive strategy in future adjuvant therapy along with DTX chemotherapy.
Keywords: Breast cancer; Chemotherapy; Docetaxel; STARD10; miR-638.
Copyright © 2017 Elsevier Inc. All rights reserved.