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Altered expression of miR-181a and miR-146a does not change the expression of surface NCRs in human NK cells

机译:miR-181a和miR-146a的表达改变不会改变人NK细胞中表面NCR的表达

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摘要

MicroRNAs (miRNAs) play an important role in regulating gene expression and immune responses. Of interest, miR-181a and miR-146a are key players in regulating immune responses and are among the most abundant miRNAs expressed in NK cells. Bioinformatically, we predicted miR-181a to regulate the expression of the natural cytotoxicity receptor NCR2 by seeded interaction with the 3′-untranslated region (3′-UTR). Whereas, miR-146a expression was not significantly different (P = 0.7361), miR-181a expression was, on average 10-fold lower in NK cells from breast cancer patients compared to normal subjects; P < 0.0001. Surface expression of NCR2 was detected in NK cells from breast cancer patients (P = 0.0384). While cytokine receptor-induced NK cell activation triggered overexpression of miR-146a when stimulated with IL-2 (P = 0.0039), IL-15 (P = 0.0078), and IL-12/IL-18 (P = 0.0072), expression of miR-181a was not affected. Overexpression or knockdown of miR-181a or miR-146a in primary cultured human NK cells did not affect the level of expression of any of the three NCRs; NCR1, NCR2 or NCR3 or NK cell cytotoxicity. Expression of miR-181a and miR-146a did not correlate to the expression of the NCRs in NK cells from breast cancer patients or cytokine-stimulated NK cells from healthy subjects.
机译:微小RNA(miRNA)在调节基因表达和免疫反应中起重要作用。有趣的是,miR-181a和miR-146a是调节免疫反应的关键因素,并且是NK细胞中表达最丰富的miRNA之一。在生物信息学上,我们预测miR-181a通过与3'-非翻译区(3'-UTR)的种子相互作用来调节天然细胞毒性受体NCR2的表达。与正常人相比,乳腺癌患者NK细胞中miR-146a的表达没有显着差异(P = 0.7361),miR-181a的表达平均低10倍; P <0.0001。在乳腺癌患者的NK细胞中检测到NCR2的表面表达(P = 0.0384)。当由IL-2(P = 0.0039),IL-15(P = 0.0078)和IL-12 / IL-18(P = 0.0072)刺激时,细胞因子受体诱导的NK细胞活化会触发miR-146a的过表达。 miR-181a的数量不受影响。原代培养的人NK细胞中miR-181a或miR-146a的过表达或敲低并不影响这三个NCR中任何一个的表达水平。 NCR1,NCR2或NCR3或NK细胞的细胞毒性。 miR-181a和miR-146a的表达与乳腺癌患者NK细胞或健康受试者的细胞因子刺激的NK细胞中NCR的表达不相关。

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