Downregulation of lncRNA GAS5 confers tamoxifen resistance by activating miR-222 in breast cancer

Long noncoding RNAs (lncRNAs) work as oncogenes or tumor suppressors that play important roles in tumorigenesis and chemotherapeutic drug resistance. This study investigates the role of lncRNA growth arrest-specific transcript 5 (GAS5) in tamoxifen resistance in breast cancer. A microarray of lncRNAs was screened in tamoxifen-resistant MCF-7R cells and the parental, non-resistant MCF-7 cells. Downregulation of lncRNA GAS5 was found in MCF-7R cells. Besides, decreased expression of GAS5 was found in breast cancer tissues, which was associated with advanced TNM stage and shorter overall survival time. We further found that GAS5 overexpression enhanced cell sensitivity to tamoxifen in MCF-7R cells both in vitro and in vivo. Moreover, GAS5 increased sensitivity of breast cancer cells to tamoxifen by serving as a molecular sponge for miR-222, contributing to suppression of phosphatase and tensin homologs (PTEN) (one endogenous target of miR-222). Collectively, our study demonstrates that GAS5 enhances the efficacy of tamoxifen in the treatment of breast cancer and could be a novel prognostic biomarker.