PTEN公司
癌症研究
PI3K/AKT/mTOR通路
蛋白激酶B
微泡
肿瘤微环境
转移
外体
生物
肿瘤进展
巨噬细胞极化
小RNA
信号转导
化学
细胞生物学
癌症
巨噬细胞
体外
肿瘤细胞
基因
生物化学
遗传学
作者
Tengfei Chen,Yali Liu,Chang Li,C. F. Xu,Cheng Ding,Jun Chen,Cheng Ding
标识
DOI:10.1016/j.ctarc.2021.100412
摘要
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 activated the PI3K/AKT signaling pathway. In addition, eIF4A3 promoted circRNA biogenesis and cyclization by binding to its flanking sequences. Exosomal circFARSA plays a crucial role in cross-talk between macrophages and NSCLC cells through the PTEN/PI3K/AKT signaling pathway, and is a promising diagnostic/prognostic biomarker for NSCLC.
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