miR-9 modulates the expression of interferon-regulated genes and MHC class I molecules in human nasopharyngeal carcinoma cells
miR-9 modulates the expression of interferon-regulated genes and MHC class I molecules in human nasopharyngeal carcinoma cells
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miR-9 调节人鼻咽癌细胞中干扰素调节基因和 MHC I 类分子的表达。
DOI：
10.1016/j.bbrc.2012.12.097
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发表时间：
2013-02-15
影响因子：
3.1
通讯作者：
Xiao, Dong
中科院分区：
文献类型：
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作者：
Gao, Fei;Zhao, Zun-Lan;Xiao, Dong
近年来发现miR-9在某些肿瘤中的作用涉及细胞增殖、上皮-间质转化（EMT）、侵袭转移、细胞凋亡和肿瘤血管生成等。miR-9在鼻咽癌中普遍下调，但其在鼻咽癌发病机制中的确切作用尚不清楚。因此，我们首先使用表达miR-9的CNE 2细胞，通过微阵列分析来确定miR-9过表达对整体基因表达谱的影响。基于微阵列的基因表达数据出乎意料地证明了大量上调或下调的免疫和炎症相关基因，包括许多众所周知的干扰素（IFN）诱导的基因（例如，IFI 44 L、PSMB 8、IRF 5、PSMB 10、IFI 27、PSB9_HUMAN、IFIT 2、TRAIL、IFITI、PSB8_HUMAN、IRFI、B2 M和GBP 1）、主要组织相容性复合体（MHC）I类分子（例如，HLA-B、HLA-C、HLA-F和HLA-H）和白细胞介素（IL）相关基因（例如，IL 2 ORB、GALT、IL 7、IL 1B、IL 1 I、IL 1F 8、伊利亚、IL 6和IL 7 R），其通过qRT-PCR确认。此外，miR-9与miRNA模拟物的过表达显著上调或下调了上述IFN诱导基因、MHC I类分子和IL相关基因的表达;相反，在CNE 2和5- 8 F细胞中，miR-9抑制剂相应地降低或增加了上述免疫和炎症相关基因。综上所述，这些发现首次证明了miR-9可以调节人类癌细胞中IFN诱导的基因和MHC I类分子的表达，表明miR-9在连接炎症和癌症中的新作用，这仍有待充分表征。(C)2013 Elsevier Inc. All rights reserved.
The functions of miR-9 in some cancers are recently implicated in regulating proliferation, epithelial-mesenchymal transition (EMT), invasion and metastasis, apoptosis, and tumor angiogenesis, etc. miR-9 is commonly down-regulated in nasopharyngeal carcinoma (NPC), but the exact roles of miR-9 dysregulation in the pathogenesis of NPC remains unclear. Therefore, we firstly used miR-9-expressing CNE2 cells to determine the effects of miR-9 overexpression on global gene expression profile by microarray analysis. Microarray-based gene expression data unexpectedly demonstrated a significant number of up-or down-regulated immune- and inflammation-related genes, including many well-known interferon (IFN)-induced genes (e.g., IFI44L, PSMB8, IRF5, PSMB10, IFI27, PSB9_HUMAN, IFIT2, TRAIL, IFITI, PSB8_HUMAN, IRFI, B2M and GBP1), major histocompatibility complex (MHC) class I molecules (e.g., HLA-B, HLA-C, HLA-F and HLA-H) and interleukin (IL)-related genes (e.g., IL2ORB, GALT, IL7, IL1B, ILI I, IL1F8, ILIA, IL6 and IL7R), which was confirmed by qRT-PCR. Moreover, the overexpression of miR-9 with the miRNA mimics significantly up- or down-regulated the expression of above-mentioned IFN-inducible genes, MHC class I molecules and IL-related genes; on the contrary, miR-9 inhibition by anti-miR-9 inhibitor in CNE2 and 5-8F cells correspondingly decreased or increased the aforementioned immune- and inflammation-related genes. Taken together, these findings demonstrate, for the first time, that miR-9 can modulate the expression of IFN-induced genes and MHC class I molecules in human cancer cells, suggesting a novel role of miR-9 in linking inflammation and cancer, which remains to be fully characterized. (C) 2013 Elsevier Inc. All rights reserved.