Identification and Analysis of Estrogen Receptor <i>α</i> Promoting Tamoxifen Resistance‐Related lncRNAs

Abstract

70-75% breast cancer patients are estrogen receptor alpha positive (ER<i>α</i>+), and the antiestrogen drug tamoxifen has been used for the past three decades. However, in 20-30% of these patients, tamoxifen therapy fails due to intrinsic or acquired resistance. A previous study has showed ER<i>α</i> signaling still exerts significant roles in the development of tamoxifen resistance and several lncRNAs have been demonstrated important roles in tamoxifen resistance. But ER<i>α</i> directly regulated and tamoxifen resistance related lncRNAs remain to be discovered. We reanalyze the published ER<i>α</i> chromatin immunoprecipitation-seq (ChIP-seq) and RNA-seq data of tamoxifen-sensitive (MCF-7/WT) and tamoxifen-resistant (MCF-7/TamR) breast cancer cells. We demonstrate that there are differential ER<i>α</i> recruitment events and the differentials may alert the expression profile in MCF-7/WT and MCF-7/TamR cells. Furthermore, we make an overlap of the ER<i>α</i> binding lncRNAs and differentially expressed lncRNAs and get 49 ER<i>α</i> positively regulated lncRNAs. Among these lncRNAs, the expression levels of AC117383.1, AC144450.1, RP11-15H20.6, and ATXN1-AS1 are negatively correlated with the survival probability of breast cancer patients and ELOVL2-AS1, PCOLCE-AS1, ITGA9-AS1, and FLNB-AS1 are positively correlated. These lncRNAs may be potential diagnosis or prognosis markers of tamoxifen resistance.