Resveratrol promotes MICA/B expression and natural killer cell lysis of breast cancer cells by suppressing c-Myc/miR-17 pathway.
Resveratrol promotes MICA/B expression and natural killer cell lysis of breast cancer cells by suppressing c-Myc/miR-17 pathway.
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DOI：
10.18632/oncotarget.19445
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发表时间：
2017-09-12
期刊：
影响因子：
--
通讯作者：
Fan W
中科院分区：
文献类型：
--
作者：
Pan J;Shen J;Si W;Du C;Chen D;Xu L;Yao M;Fu P;Fan W
主要组织相容性复合物I类链相关蛋白A和B（云母和MIC B）是免疫效应细胞识别肿瘤细胞的重要配体。在这里，我们报告白藜芦醇上调乳腺癌细胞中云母和MICB的蛋白质和mRNA表达，这反过来又促进了乳腺癌细胞溶解自然杀伤（NK）细胞在体外和体内。针对NK 2组成员D的抗体阻断了这种作用。发现云母和MICB的3′-非翻译区是miR-17的直接结合靶点。在用miR-17抑制剂或模拟物转染的乳腺癌细胞中，云母和MICB表达分别增加或减少。C-Myc过表达/敲低增加/减少miR-17-92簇宿主基因的转录。白藜芦醇抑制c-Myc表达，从而抑制miR-17-92簇的转录，从而下调miR-17。在两组乳腺癌标本中，miR-17表达与云母和MICB表达和总生存率呈负相关。因此，白藜芦醇通过抑制乳腺癌细胞中的c-Myc/miR-17途径上调云母和MICB，并增加NK细胞对乳腺癌细胞的细胞溶解。这表明白藜芦醇具有促进乳腺癌患者抗肿瘤免疫反应的潜力。
Major histocompatibility complex class I chain-related proteins A and B (MICA and MICB) are important ligands for recognition of tumor cells by immune effector cells. Here, we report that resveratrol upregulated the protein and mRNA expression of MICA and MICB in breast cancer cells, which in turn promoted breast cancer cell lysis by natural killer (NK) cells in vitro and in vivo. Antibodies against NK group 2 member D blocked this effect. The 3′-untranslated regions of MICA and MICB were found to be direct binding targets of miR-17. MICA and MICB expression increased or decreased in breast cancer cells transfected with a miR-17 inhibitor or mimic, respectively. C-Myc overexpression/knockdown increased/decreased transcription of the miR-17-92 cluster host gene. Resveratrol suppressed c-Myc expression, which inhibited the transcription of miR-17-92 cluster, thereby downregulating miR-17. MiR-17 expression correlated inversely with MICA and MICB expression and overall survival in two sets of breast cancer specimens. Resveratrol thus upregulates MICA and MICB by suppressing the c-Myc/miR-17 pathway in breast cancer cells, and increases the cytolysis of breast cancer cells by NK cells. This suggests resveratrol has the potential to promote antitumor immune responses in breast cancer patients.
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影响因子：
16.6
作者：
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影响因子：
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发表时间：
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作者：
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