MicroRNA profiling of CD3+ CD56+ cytokine-induced killer cells.
MicroRNA profiling of CD3+ CD56+ cytokine-induced killer cells.
复制标题
CD3( )CD56( ) 细胞因子诱导的杀伤细胞的 MicroRNA 分析
DOI：
10.1038/srep09571
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发表时间：
2015-03-31
影响因子：
4.6
通讯作者：
Hou Z
中科院分区：
文献类型：
--
作者：
Wang W;Li R;Meng M;Wei C;Xie Y;Zhang Y;Jiang L;Dong R;Wang C;Zhong Y;Yang F;Tang W;Jin X;Liu B;Hou Z
研究表明，IL-2和IL-15在CIK细胞制备过程中表现出不同的作用。通过使用微阵列，我们分析了PBMC、CIKIL-2和CIKIL-15的miRNA表达谱。通过生物信息学分析，寻找调控CIK细胞增殖和抗肿瘤活性的关键miRNAs。我们在PBMC和CIKIL-2之间鉴定了261个差异表达的miRNA（DEM），在PBMC和CIKIL-15之间鉴定了249个DEM。miR-143- 3 p/miR-145- 5 p是可能正调控细胞增殖的miRNA簇。相反，miR-340- 5 p/miR-340- 3 p簇可能通过诱导细胞凋亡负调控细胞增殖，这可能导致CIKIL-2的细胞增殖能力下降。miRNA-靶标相互作用分析表明，10种共下调的miRNA可以协同地开启CIK细胞中肿瘤细胞毒性基因库的表达。CIKIL-2和CIKIL-15之间的DEM可能有助于增强CIKIL-2的肿瘤细胞毒能力。更重要的是，我们发现被抑制的miR-193 a-5 p可以调节抑制性受体KLRD 1的表达。验证试验的结果表明，KLRD 1在CIK细胞中上调。我们的研究结果为CIK细胞的产生机制和肿瘤细胞毒作用提供了新的见解，并为临床试验的安全性提供了依据。
Studies have proven that IL-2 and IL-15 showed contrasting roles during CIK cells preparation. By employing microarray, we analyzed miRNA expression profiles of PBMC, CIKIL-2 and CIKIL-15. Advanced bioinformatic analyses were performed to explore the key miRNAs which may regulate cell proliferation and anti-tumor activity of CIK. We identified 261 differentially expressed miRNAs (DEMs) between PBMC and CIKIL-2, and 249 DEMs between PBMC and CIKIL-15. MiR-143-3p/miR-145-5p was miRNA cluster which may positively regulate cell proliferation. In contrast, miR-340-5p/miR-340-3p cluster may negatively regulate cell proliferation via induction apoptosis, which may cause decreased cell proliferation capacity of CIKIL-2. MiRNA-target interaction analysis indicated that 10 co-downregulated miRNAs may synergistically turn on the expression of a pool of tumor cytotoxic genes in CIK cells. The DEMs between CIKIL-2 and CIKIL-15 may contribute to enhanced tumor cytotoxic capacity of CIKIL-2. Importantly, we found that repressed miR-193a-5p may regulate the expressions of inhibitory receptor KLRD1. The results of the validation assay have shown that KLRD1 were upregulated in CIK cells. Our findings have provided new insights into mechanisms of CIK cells production and tumor cytotoxic function, and shed light on their safety for clinical trial.