FBI-1 enhanced the resistance of triple-negative breast cancer cells to chemotherapeutic agents via the miR-30c/PXR axis

Hua Yang,Aimin Zang,Yaning Wei,Lili Ren,Xuebing Bi,Qian Zhang,Guanghai Dai,Youchao Jia,Ming Wen,Xiaoli Li,Yanan Wang,Yumiao Li,Yang Yang

doi:10.1038/s41419-020-03053-0

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.

Highlights

FBI‐1, named leukemia/lymphoma‐related factor (LRF), osteoclast‐derived zinc finger (OCZF), Pokemon, or Zinc finger and BTB domain-containing protein 7A (ZBTB7A), has been considered an important proto‐oncogene and plays important roles in human malignancies[1,2,3]
FBI-1 enhanced the activation of the pregnane X receptor (PXR) signaling pathway
FBI-1 enhanced the resistance of triple-negative breast cancer (TNBC) patientsderived cells (PDCs) to olaparib by accelerating its elimination or clearance in cells by the miR-30c/PXR axis

Summary

Introduction

FBI‐1 (factor that binds to inducer of short transcripts‐1), named leukemia/lymphoma‐related factor (LRF), osteoclast‐derived zinc finger (OCZF), Pokemon, or Zinc finger and BTB domain-containing protein 7A (ZBTB7A), has been considered an important proto‐oncogene and plays important roles in human malignancies[1,2,3]. FBI-1 can promote the proliferation or metastasis of human cancer cells (HCC) by repressing tumor suppressors but can induce the resistance of HCC cells to antitumor agents. Breast cancer can be divided into endocrine-dependent breast cancer, HER2-. Endocrine-dependent breast cancer and HER2-positive breast cancer have drugs for symptomatic relief (e.g., Tamoxifen and Trastuzumab, respectively), and patients have a relatively good prognosis, while TNBC patients have strong heterogeneity[11,12,13,14,15]. It is of great significance to study and discover new intervention targets for anti-tumor treatment of TNBC and to research and develop more effective antitumor treatment strategies for this kind of cancer

Methods

Results

Conclusion