LncRNA GNAS-AS1 facilitates ER+ breast cancer cells progression by promoting M2 macrophage polarization via regulating miR-433-3p/GATA3 axis

作者：Shiqin Liu, Zhiyang Zhou, Xue Dong, Lei Guo, Kejing Zhang · 发表于：Bioscience Reports · 年份：2020 · DOI：10.1042/bsr20200626 · 被引用次数：61 · 研究领域：Immune cells in cancer、Ferroptosis and cancer prognosis、Epigenetics and DNA Methylation

OBJECTIVE: ER+ breast cancer is the most common type of breast cancer, which seriously affects the physical and mental health of women. Recently, lncRNAs mediated tumor-associated macrophages (TAM) were identified to involve in tumorigenesis. Therefore, the present study aimed at demonstrating the regulatory network of GNAS-AS1 in TAM-mediated ER+ breast cancer progress. METHODS: The expression levels of genes were evaluated using qRT-PCR. The proportions of polarized macrophages (M1, M2) were assessed by flow cytometry. Cell proliferation, migration and invasion were evaluated by CCK-8, wound healing and transwell assay, respectively. Double-luciferase reporter system was used to detect the interaction between molecules. Western blot was applied to test protein levels. RESULTS: The expression of GNAS-AS1 was obviously increased in ER+ breast cancer tissues and cell lines, as well as M2 macrophages. GNAS-AS1 facilitated the capabilities of proliferation, migration and invasion of ER+ breast cancer cells by accelerating M2 macrophage polarization via directly sponging miR-433-3p. GATA3, as a target of miR-433-3p, could positively regulate by GNAS-AS1. Furthermore, either miR-433-3p overexpression or GATA3 knockdown impaired the effects of GNAS-AS1 on M2 macrophage polarization and ER+ breast cancer cells progression. CONCLUSION: GNAS-AS1/miR-433-3p/GATA3 axis promoted proliferation, metastasis of ER+ breast cancer cells by accelerating M2 macrophage polarization. The mechanism...