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首页> 外文期刊>Cellular Signalling >Interleukin 6 induces cell proliferation of clear cell renal cell carcinoma by suppressing hepaCAM via the STAT3-dependent up-regulation of DNMTI or DNMT3b
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Interleukin 6 induces cell proliferation of clear cell renal cell carcinoma by suppressing hepaCAM via the STAT3-dependent up-regulation of DNMTI or DNMT3b

机译：白细胞介素6通过DNMTI或DNMT3B的STAT3依赖性上调抑制Hepacam来诱导透明细胞肾细胞癌的细胞增殖

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摘要

Interleukin 6 (IL-6), a tumor promoting cytokine, has been largely implicated in the development of renal cell carcinoma (RCC). Hepatocyte cell adhesion molecule (hepaCAM) is a novel tumor suppressor, which is lost or down regulated in many cancer types including RCC. In the present study, we intensively investigated the connection between IL-6 and hepaCAM in RCC. Our analysis of RCC tissues, adjacent tissues and paired serum samples from RCC patients revealed that IL-6 was elevated in patient serum and RCC tissue, whereas hepaCAM was completely lost or significantly down-regulated. Furthermore, we observed an association between IL-6 increase and hepaCAM decrease in RCC tissue samples. In the section of cytological researches, we found in RCC cell lines that IL-6 was a direct upstream regulator of hepaCAM, and that hepaCAM down-regulation was involved in IL-6 driven cell proliferation. We also demonstrated that IL-6-mediated promoter hypermethylation largely accounted for the hepaCAM loss in RCC, and it was STAT3-dependent. Additionally, our data showed that DNMT1 up-regulation induced by IL-6/STAT3 signaling was indispensable for IL-6-mediated hepaCAM loss in RCC cell lines ACHN and 769-P, while DNMT3b up-regulation was crucial for hepaCAM loss in A498. Our findings provide a novel signal pathway regulating cell proliferation, potentially representing a therapeutic target for RCC. (C) 2017 Elsevier Inc. All rights reserved.
机译：白细胞介素6（IL-6）是一种促肿瘤细胞因子，在很大程度上与肾细胞癌（RCC）的发生有关。肝细胞粘附分子（hepaCAM）是一种新型的肿瘤抑制因子，在包括肾细胞癌在内的多种癌症中丢失或下调。在本研究中，我们深入研究了肾细胞癌中IL-6与hepaCAM之间的关系。我们对肾细胞癌组织、邻近组织和肾细胞癌患者配对血清样本的分析显示，患者血清和肾细胞癌组织中IL-6升高，而hepaCAM完全消失或显著下调。此外，我们在肾细胞癌组织样本中观察到IL-6增加与hepaCAM减少之间的关联。在细胞学研究部分，我们在RCC细胞系中发现，IL-6是hepaCAM的直接上游调节因子，hepaCAM的下调参与了IL-6驱动的细胞增殖。我们还证明，IL-6介导的启动子甲基化在很大程度上解释了RCC中hepaCAM的丢失，并且它依赖于STAT3。此外，我们的数据显示，IL-6/STAT3信号诱导的DNMT1上调对于IL-6介导的肾癌细胞系ACHN和769-P的hepaCAM丢失是必不可少的，而DNMT3b上调对于A498的hepaCAM丢失是至关重要的。我们的发现提供了一种新的调节细胞增殖的信号通路，可能代表RCC的治疗靶点。（C） 2017爱思唯尔公司版权所有。

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