LncRNA DUXAP8 Induces Breast Cancer Radioresistance by Modulating the PI3K/AKT Pathway and the EZH2-E-Cadherin/RHOB Pathway

Abstract

BackgroundRadiation resistance poses a major clinical challenge in breast cancer (BC) treatment, but little is known about how long noncoding RNA (lncRNA) may regulate this phenomenon. We aimed to explore the role and possible mechanisms of lncRNA DUXAP8 in radiotherapy resistance of BC. Methods We used gain-of-function and loss-of-function assays to examine the impact of DUXAP8 on the radiosensitivity of BC cells. We performed RNA immunoprecipitation and chromatin immunoprecipitation assays to determine the potential mechanisms of DUXAP8. Results Here, we reported that DUXAP8 was highly expressed in radioresistant BC tissues, and high expression of DUXAP8 was associated with poor prognosis. We found that the overexpression of DUXAP8 promoted radioresistance, while inhibition of DUXAP8 expression increased radiosensitivity. Further studies revealed that DUXAP8 enhanced the radioresistance of BC cells by activating the PI3K/AKT pathway and by repressing the expression of E-cadherin and RHOB through interaction with EZH2. Moreover, DUXAP8 depletion significantly improved the radiosensitivity of BC in vivo. Conclusions Together, our work demonstrates for the first time, the ability of DUXAP8 to promote radiation resistance through modulating the PI3K/AKT pathway and the EZH2-E-cadherin/RHOB pathway.