STAT6 phosphorylation upregulates microRNA-155 expression and subsequently enhances the pathogenesis of chronic lymphocytic leukemia
STAT6 phosphorylation upregulates microRNA-155 expression and subsequently enhances the pathogenesis of chronic lymphocytic leukemia
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STAT6磷酸化上调microRNA-155表达并随后增强慢性淋巴细胞白血病的发病机制
DOI：
10.3892/ol.2019.10294
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发表时间：
2019-07-01
期刊：
影响因子：
2.9
通讯作者：
Wang, Xin
中科院分区：
文献类型：
--
作者：
Chen, Na;Feng, Lili;Wang, Xin
慢性淋巴细胞性白血病（CLL）是一种CD 5（+）B细胞的克隆性扩增，是成人白血病的最常见形式;然而，其发病机制的分子机制仍不确定。以前已经提出，许多生物因子，包括细胞因子，可能参与恶性细胞的增殖。例如，白细胞介素（IL）-4、IL-2、干扰素-γ和肿瘤坏死因子作为细胞凋亡的抑制剂发挥作用;而IL-5和IL-10是细胞凋亡的诱导剂。本研究结果表明，IL-4以时间依赖的方式诱导信号转导子和转录激活子6（STAT 6）的磷酸化和激活。值得注意的是，在用IL-4处理后，MEC-1细胞中microRNA（miR）-155的表达水平增加;然而，这种作用在通过RNA干扰敲低STAT 6后减弱。此外，STAT 6敲低促进细胞凋亡，这部分减弱了用IL-4处理。尽管存在IL-4，但抑制miR-155表达显著增加细胞凋亡。本研究的结果表明，用IL-4处理增强了miR-155的表达，miR-155通过增强STAT 6的磷酸化来调节CLL细胞存活。
Chronic lymphocytic leukemia (CLL), a clonal expansion of CD5(+) B cells, is the most common form of adult leukemia; however, the molecular mechanisms underlying its pathogenesis remain undetermined. It has been previously suggested that numerous biological factors, including cytokines, may be involved in the proliferation of malignant cells. For example, interleukin (IL)-4, IL-2, interferon-gamma and tumor necrosis factor serve roles as inhibitors of cellular apoptosis; whereas IL-5 and IL-10 are inducers of cellular apoptosis. In the present study, the results demonstrated that the phosphorylation and activation of signal transducer and activator of transcription 6 (STAT6) was induced by IL-4 in a time-dependent manner. Notably, the expression level of microRNA (miR)-155 was increased in MEC-1 cells following treatment with IL-4; however, this effect was attenuated following STAT6 knockdown via RNA interference. In addition, STAT6 knockdown promoted cell apoptosis, which was partly attenuated by treatment with IL-4. Inhibition of miR-155 expression significantly increased cell apoptosis despite the presence of IL-4. The results of the present study suggested that treatment with IL-4 enhanced the expression of miR-155, which regulated CLL cell survival via the enhanced phosphorylation of STAT6.