Long Non-Coding RNA PVT1 Regulates the Resistance of the Breast Cancer Cell Line MDA-MB-231 to Doxorubicin via Nrf2

Abstract

Triple-negative breast cancer (TNBC) is one of the most common malignant tumor types in females and its drug resistance is a major clinical issue. An increasing number of long non-coding RNAs (lncRNAs) have been reported as key regulators of drug resistance in TNBC. Plasmacytoma variant translocation 1 (PVT1) has been proved to promote the development of various cancer types. The present study suggested that PVT1 enhances the resistance of the TNBC cell line MDA-MB-231 to doxorubicin and uncovered the molecular mechanism. PVT1 function assays and its target gene analyses were performed. We revealed that PVT1 promoted the protein stability of nuclear factor erythroid 2 like 2 (Nrf2) by inhibiting the binding of kelch-like ECH-associated protein 1 (Keap1) to Nrf2, which is beneficial to the resistance of MDA-MB-231 cells to doxorubicin. These novel results enhance the current knowledge regarding the versatile roles of PVT1 and lay a foundation for future developments of clinical applications.