Lautenberg Center for General and Tumor Immunology, The Hebrew University, The BioMedical Research Institute, Hadassah Medical School, Jerusalem, Israel.
Cancer Res. 2012 Nov 1;72(21):5463-72. doi: 10.1158/0008-5472.CAN-11-2671. Epub 2012 Aug 21.
Natural killer cells (NK) are a component of innate immunity well known for their potent ability to kill virus-infected or neoplastically transformed cells following stimulation of the NK cell receptor NKG2D. One of the various ligands of NKG2D is MICB, a stress-induced ligand that has been found to be upregulated on the surface of tumor cells. However, there is little knowledge about how this upregulation may occur or how it may be selected against in tumors as a mechanism of immune escape. Here, we report that the metastasis-associated microRNA (metastamir) miR-10b directly binds to the 3' untranslated region of MICB and downregulates its expression. Notably, antagonizing miR-10b action enhanced NKG2D-mediated killing of tumor cells in vitro and enhanced clearance of tumors in vivo. Conversely, overexpression of miR-10b downregulated MICB and impaired elimination of tumor cells. Together, our results define MICB as a novel immune target of miR-10b, implying a direct link between metastasis capability and immune escape from NK cells.
自然杀伤细胞（NK）是先天免疫系统的一个组成部分，其显著特点是在受到 NK 细胞受体 NKG2D 的刺激后，能够有效地杀死被病毒感染或发生恶性转化的细胞。NKG2D 的多种配体之一是 MICB，这是一种应激诱导的配体，已发现在肿瘤细胞表面上调。然而，关于这种上调是如何发生的，以及它如何作为一种免疫逃避机制在肿瘤中被选择，人们知之甚少。在这里，我们报告说，转移相关 microRNA（metastamir）miR-10b 直接结合 MICB 的 3'非翻译区并下调其表达。值得注意的是，拮抗 miR-10b 的作用增强了体外 NKG2D 介导的杀伤肿瘤细胞的作用，并增强了体内肿瘤的清除。相反，miR-10b 的过表达下调了 MICB，并损害了肿瘤细胞的消除。总之，我们的研究结果将 MICB 定义为 miR-10b 的一个新的免疫靶点，表明转移能力与 NK 细胞的免疫逃避之间存在直接联系。
