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

作者：Gu, Juan; Wang, Yueping; Wang, Xuedong^*; Zhou, Daoping; Shao, Chaopeng; Zhou, Ming; He, Zhimin

来源：Cancer Letters, 2018, 434: 1-10.

DOI：10.1016/j.canlet.2018.06.039

• LncRNA GAS5
• MiR-222
• Breast cancer
• Tamoxifen
• Drug resistance

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 IncRNA 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 over expression 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.

• 出版日期2018
• 单位深圳市第二人民医院; 广州医科大学; 南京医科大学; 安徽医科大学; 江南大学; 中南大学