The Mechanisms of lncRNA-Mediated Multidrug Resistance and the Clinical Application Prospects of lncRNAs in Breast Cancer

SIMPLE SUMMARY: Multidrug resistance (MDR) is a major cause of breast cancer (BC) chemotherapy failure. Long noncoding RNAs (lncRNAs) have been shown closely related to the chemoresistance of BC. In this work, the mechanisms of lncRNA-mediated MDR in BC were elaborated from eight sections, including apoptosis, autophagy, DNA repair, cell cycle, drug efflux, epithelial-mesenchymal transition, epigenetic modification and the tumor microenvironment. Additionally, we also discuss the clinical significance of lncRNAs, which may be biomarkers for diagnosis, therapy and prognosis. ABSTRACT: Breast cancer (BC) is a highly heterogeneous disease and presents a great threat to female health worldwide. Chemotherapy is one of the predominant strategies for the treatment of BC; however, multidrug resistance (MDR) has seriously affected or hindered the effect of chemotherapy. Recently, a growing number of studies have indicated that lncRNAs play vital and varied roles in BC chemoresistance, including apoptosis, autophagy, DNA repair, cell cycle, drug efflux, epithelial-mesenchymal transition (EMT), epigenetic modification and the tumor microenvironment (TME). Although thousands of lncRNAs have been implicated in the chemoresistance of BC, a systematic review of their regulatory mechanisms remains to be performed. In this review, we systematically summarized the mechanisms of MDR and the functions of lncRNAs mediated in the chemoresistance of BC from the latest literature. These findings significantly enhance the current understanding of lncRNAs and suggest that they may be promising prognostic biomarkers for BC patients receiving chemotherapy, as well as therapeutic targets to prevent or reverse chemoresistance.