Cancer-derived Circulating MicroRNAs Promote Tumor Angiogenesis by Entering Dendritic Cells to Degrade Highly Complementary MicroRNAs.
Cancer-derived Circulating MicroRNAs Promote Tumor Angiogenesis by Entering Dendritic Cells to Degrade Highly Complementary MicroRNAs.
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癌症来源的循环 MicroRNA 通过进入树突状细胞降解高度互补的 MicroRNA 来促进肿瘤血管生成
作者：
Wang J;Ye H;Zhang D;Cheng K;Hu Y;Yu X;Lu L;Hu J;Zuo C;Qian B;Yu Y;Liu S;Liu G;Mao C;Liu S
了解癌细胞和免疫细胞之间的相互作用将激发新的癌症治疗策略。然而，癌症来源的循环miRNA如何调节这种相互作用仍不清楚。在这里，我们发现前列腺癌细胞分泌的循环miR-410- 5 p在argonaute-2蛋白的帮助下进入树突状细胞（DC）。癌细胞抗原刺激DC产生miR-410- 3 p，miR-410- 3 p是来源于pre-miR-410的miR-410- 5 p的高度互补的对应物。DC内化的miR-410- 5 p通过碱基配对降解miR-410- 3 p，从而抑制其抑制肿瘤血管生成、促进肿瘤生长的功能。此外，阻断miR-410- 5 p上调miR-410- 3 p以抑制肿瘤生长。我们的工作表明了免疫细胞在癌症进展中的新的miRNA介导的作用，以及通过抑制循环miRNA来治疗癌症的新策略。
Understanding the interaction between cancer cells and immunocytes will inspire new cancer therapy strategies. However, how cancer-derived circulating miRNAs modulate such interaction remains unclear. Here we discovered that circulating miR-410-5p, secreted by prostate cancer cells, entered dendritic cells (DCs), with the aid of argonaute-2 protein. The cancer cell antigens stimulated the DCs to produce miR-410-3p, a highly complementary counterpart of miR-410-5p derived from pre-miR-410. The DC-internalized miR-410-5p degraded the miR-410-3p by base pairing and thus inhibited its function in suppressing tumor angiogenesis, promoting tumor growth. Furthermore, blockade of the miR-410-5p upregulated the miR-410-3p to inhibit tumor growth. Our work suggests a new miRNA-mediated role of immunocytes in cancer progression and a new strategy of cancer therapy through suppressing circulating miRNAs.