FBI-1 enhanced the resistance of triple-negative breast cancer cells to chemotherapeutic agents via the miR-30c/PXR axis
Hua Yang, Lili Ren, Yanan Wang, Xuebing Bi, Xiaoli Li, Ming Wen, Qian Zhang, Yang Yang, Youchao Jia, Yumiao Li, Aimin Zang, Yaning Wei, Guanghai Dai
Abstract
The factor that binds to the inducer of short transcripts-1 (FBI-1) is a transcription suppressor and an important proto-oncogene that plays multiple roles in carcinogenesis and therapeutic resistance. In the present work, our results indicated that FBI-1 enhanced the resistance of triple-negative breast cancer (TNBC) cells to chemotherapeutic agents by repressing the expression of micoRNA-30c targeting the pregnane X receptor (PXR). The expression of FBI-1 was positively related to PXR and its downstream drug resistance-related genes in TNBC tissues. FBI-1 enhanced the expression of PXR and enhanced the activation of the PXR pathway. The miR-30c decreased the expression of PXR by targeting the 3'-UTR of PXR, and FBI-1 increased the expression of PXR by repressing miR-30c's expression. Through the miR-30c/PXR axis, FBI-1 accelerated the clearance or elimination of antitumor agents in TNBC cells (the TNBC cell lines or the patients derived cells [PDCs]) and induced the resistance of cells to antitumor agents. Therefore, the results indicated that the miR-30c/PXR axis participates in the FBI-1-mediated drug-resistance of TNBC cells.