| Popis: |
Background Accumulating evidence indicates that the crosstalk between tumor cells and the microenvironment influences human cancer progression. However, the expression pattern, function role in the crosstalk between tumor cells and tumor microenvironment, and underlying mechanism of lncRNAs-related tumorigenesis in breast cancer are unknown. Methods The expression lncRNA-THAP7-AS1 in breast cancer (BC) were identified by in BC tissues. The functional roles of THAP7-AS1 were confirmed by in vitro and in vivo experiments. RNA-pulldown followed by mass spectrometry, RNA Immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP) assays and luciferase reporter assay revealed the mechanisms of THAP7-AS1 in BC. RT-qPCR, ELISA assays, Flow cytometry, ChIP assays and luciferase reporter assay elucidated the crosstalk between tumor cells and (tumor-associated macrophages) TAMs. Results Here, we demonstrate that long non-coding RNA (lncRNA) THAP7-AS1 induces polarization of macrophages to the M2 phenotype in an IL-4-dependent manner, and M2 tumor-associated macrophages (TAMs) secreted IL-10, which then facilitates the progression of breast cancer (BC). Mechanistically, THAP7-AS1 promoted the combination between SNF2H, SNF2L, and BAF155 and recruited the SWI/SNF complex to the promoter of EGFR to upregulate its expression, and then induced IL-4-mediated M2 polarization of macrophages via activation of the EGFR-ELK1 signaling. Reciprocally, IL-10 released from M2 TAMs upregulates CEBP-β-dependent P300 expression, and then P300, synergistically worked with c-MYC and upregulated THAP7-AS1 expression in BC cells, which constituting a feed-forward loop between tumor cells and TAMs. Moreover, THAP7-AS1 knockdown inhibits the invasion, metastasis and M2 macrophage polarization of breast cancer in vivo. Conclusions Our study highlights the role of THAP7-AS1 in the regulation crosstalk between TAM and tumor cells in BC progression and may provide a novel therapeutic target for BC treatment. |
