Tumor-derived exosomal circFARSA mediates M2 macrophage polarization via the PTEN/PI3K/AKT pathway to promote non-small cell lung cancer metastasis.
Abstract
Exosomes in the tumor microenvironment (TME) facilitate tumor progression by enabling inter-cellular communication. Tumor cell-derived exosomes can polarize tumor-associated macrophages (TAMs) to an immunosuppressive M2 phenotype. The aim of this study was to determine the role of exosomal circFARSA in non-small cell lung cancer (NSCLC) and elucidate the underlying mechanisms. In situ circFARSA expression in NSCLC tissues was analyzed using qRT-PCR. The in vitro migration of NSCLC cells was evaluated using a transwell assay or through indirect co-culture with M2 macrophages, as appropriate. Immunoprecipitation (IP), western blotting, RNA binding protein immunoprecipitation (RIP), and RNA pull down assays were conducted for mechanistic studies. CircFARSA was significantly upregulated in NSCLC tissues, and the ectopic overexpression of circFARSA enhanced NSCLC cell metastasis. Furthermore, NSCLC cell-derived exosomal circFARSA polarized the macrophages to a M2 phenotype. The NSCLC cells co-cultured with macrophages transfected with circFARSA or pre-treated with exosomal circFARSA showed enhanced EMT and metastasis. Mechanistically, exosomal circFARSA induced M2 polarization via PTEN ubiquitination and degradation, which further a...Continue Reading
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