Restoration of miR17/20a in solid tumor cells enhances the natural killer cell antitumor activity by targeting Mekk2.
Restoration of miR17/20a in solid tumor cells enhances the natural killer cell antitumor activity by targeting Mekk2.
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DOI：
10.1158/2326-6066.cir-13-0162
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发表时间：
2014-08
影响因子：
10.1
通讯作者：
Zhang HG
中科院分区：
文献类型：
--
作者：
Jiang H;Wang P;Li X;Wang Q;Deng ZB;Zhuang X;Mu J;Zhang L;Wang B;Yan J;Miller D;Zhang HG
已经在各种人类实体癌中鉴定出异常的微小RNA（miRNA）表达。然而，肿瘤细胞中的miRNA表达水平是否对肿瘤进展有任何影响尚未确定。在这项概念验证研究中，miR-17~92 miRNA簇的高水平表达的恢复揭示了其在小鼠实体癌细胞中作为肿瘤抑制因子的功能。具体而言，在小鼠乳腺癌和结肠癌细胞中miR-17~92簇中较高水平的miR-17/20 a的基因工程表达通过Mekk 2/Mek 5/Erk 5途径抑制MHC I类（H-2D）的表达来触发自然杀伤（NK）细胞识别。使用人实体瘤样品概括小鼠肿瘤研究的结果。总之，这些数据表明miR-17/20 amiRnas通过重编程肿瘤细胞以实现NK细胞介导的细胞毒性而发挥肿瘤抑制因子的作用。
Aberrant microRNA (miRNA) expression has been identified in various human solid cancers. However, whether the levels of miRNA expression in tumor cells have any effect on tumor progression has not been determined. In this proof-of-concept study, the restoration of high-level expression of the miR-17~92 cluster of miRNAs reveals its function as a tumor suppressor in murine solid cancer cells. Specifically, genetically engineered expression of higher levels of miR-17/20a in the miR-17~92 cluster in both murine breast cancer and colon cancer cells triggered natural killer (NK) cell recognition by inhibiting the expression of MHC class I (H-2D) through the Mekk2/Mek5/Erk5 pathway. Results from the mouse tumor studies were recapitulated using samples of human solid tumors. Together, these data indicate that miR-17/20amiRnas functions as a tumor suppressor by reprogramming tumor cells for NK cell-mediated cytotoxicity.