Cancer-derived Circulating MicroRNAs Promote Tumor Angiogenesis by Entering Dendritic Cells to Degrade Highly Complementary MicroRNAs

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.