Overexpression of IL-9 induced by STAT3 phosphorylation is mediated by miR-155 and miR-21 in chronic lymphocytic leukemia
Overexpression of IL-9 induced by STAT3 phosphorylation is mediated by miR-155 and miR-21 in chronic lymphocytic leukemia
复制标题
在慢性淋巴细胞白血病中，STAT3 磷酸化诱导的 IL-9 过度表达是由 miR-155 和 miR-21 介导的。
DOI：
10.3892/or.2018.6367
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发表时间：
2018-06-01
期刊：
影响因子：
4.2
通讯作者：
Wang, Xin
中科院分区：
文献类型：
--
作者：
Chen, Na;Feng, Lili;Wang, Xin
白介素9(IL-9)既可以作为免疫反应的正性调节因子，也可以作为负性免疫调节因子，但对其在肿瘤免疫中的作用却知之甚少。慢性淋巴细胞白血病(CLL)是最常见的慢性淋巴细胞增生性疾病。研究对象为2010-2011年间的20名慢性淋巴细胞性白血病患者。分析CLL患者外周血单个核细胞(PBMC)中转录因子STAT3和差异微RNA(MiRs)的表达及磷酸化情况。在先前的研究中，我们发现CLL患者体内存在高水平的IL-9。同时，在本研究中，在CLL患者的PBMC中观察到pSTAT3、miR-155和miR-21的过度表达。为了阐明IL-9、STAT3、miR-155和miR-21之间是否存在相互作用，采用MEC-1细胞进行了进一步的研究。结果表明，MEC-1细胞培养上清液中未检测到IL-9。然而，在MEC-1细胞中可以用免疫印迹检测到IL-9蛋白。值得注意的是，在MEC-1细胞培养上清液中加入重组人IL-9(rIL-9)后，pSTAT3和IL-9的表达水平呈时间依赖性增加，并可被STAT3抑制剂阻断。MiR-155和miR-21均可促进IL-9的表达，且可被STAT3抑制剂抑制。我们的研究结果表明，CLL细胞中存在新的细胞外IL-9/pSTAT3/miR-155/miR-21/细胞内IL-9正反馈系统，为CLL的发病机制和可能的治疗策略提供了新的视角。
Interleukin-9 (IL-9) can function as both a positive and negative regulator of immune response, however the role of IL-9 in tumor immunity is poorly understood. Chronic lymphocytic leukemia (CLL) is the most common chronic lympho-proliferative disorder. Twenty CLL patients from 2010 to 2011 were recruited in the study. Expression and phosphorylation of transcription factor STAT3 and differential microRNAs (miRs) in peripheral blood mononuclear cells (PBMCs) from CLL patient samples were analyzed. In a previous study, we found a high level of IL-9 in CLL patients. Concomitantly, overexpression of pSTAT3, miR-155, and miR-21 were observed in PBMCs from CLL patients in the present study. To elucidate whether there was interaction among IL-9, STAT3, miR-155, and miR-21, MEC-1 cells were used for further study. Our results revealed that there was no detectable IL-9 in the culture medium of MEC-1 cells. However, the IL-9 protein could be detected using western blotting in MEC-1 cells. Notably, when recombinant human IL-9 (rIL-9) was added to the medium of culturing MEC-1 cells, the expression levels of pSTAT3 and IL-9 in MEC-1 cells were increased in a time-dependent manner, which could be blocked by STAT3 inhibitor. Both miR-155 and miR-21 could increase IL-9 expression, which could also be suppressed by the inhibitor of STAT3. Our data indicated that the existence of the novel 'extracellular IL-9/pSTAT3/miR-155/miR-21/intracellular IL-9' positive feedback system in CLL cells, provides a novel insight in the pathogenesis and possible therapeutic strategy of CLL.