China Medical University, Shenyang, China.
Department of Nephrology, the First Hospital of China Medical University, Shenyang, China.
Cancer Sci. 2022 Jun;113(6):1968-1983. doi: 10.1111/cas.15365. Epub 2022 Apr 26.
Studies have shown exosomal circRNAs can regulate the immune escape of tumors by carrying cancer-derived molecules. Regulatory T cells (Tregs) participate in the process of tumor immune escape. However, the mechanism by which exosomal circRNAs regulate Tregs to create a microenvironment for tumor immune escape is unclear. The effect of exosomes on the proliferation, migration, and invasion of tumor cells was evaluated by CCK-8, transwell, and wound-healing assays. The expression of circGSE1 was evaluated by real-time quantitative PCR, and the function of exosomal circGSE1 was explored by Western blot and RNA pull-down assays. In vivo animal metastasis models and bioluminescence imaging were used to verify the effect of exosomal circGSE1 on tumor progression. Collectively, we revealed that exosomal circGSE1 derived from hepatocellular carcinoma (HCC) cells promotes the progression of HCC by inducing Tregs expansion via regulating the miR-324-5p/TGFBR1/Smad3 axis. Therefore, in the future, exosomal circGSE1 can be used as a promising biomarker for immunotherapy of HCC.
研究表明，外泌体 circRNAs 可以通过携带癌症来源的分子来调节肿瘤的免疫逃逸。调节性 T 细胞（Tregs）参与肿瘤免疫逃逸的过程。然而，外泌体 circRNAs 通过调节 Tregs 来创建肿瘤免疫逃逸微环境的机制尚不清楚。通过 CCK-8、transwell 和划痕愈合实验评估外泌体对肿瘤细胞增殖、迁移和侵袭的影响。通过实时定量 PCR 评估 circGSE1 的表达，并通过 Western blot 和 RNA 下拉实验探索外泌体 circGSE1 的功能。使用体内动物转移模型和生物发光成像来验证外泌体 circGSE1 对肿瘤进展的影响。总之，我们揭示了源自肝细胞癌（HCC）细胞的外泌体 circGSE1 通过调节 miR-324-5p/TGFBR1/Smad3 轴诱导 Tregs 扩增，从而促进 HCC 的进展。因此，在未来，外泌体 circGSE1 可以作为 HCC 免疫治疗的有前途的生物标志物。
