BackgroundEmerging evidence shows that Hippo signal pathways can regulate the progression of various cancer. While the roles of Yes-associated protein (YAP), the key transducer of Hippo signals, in the development of endometrial cancer (EC) are rarely investigated.MethodsThe expression of YAP in endometrial cancer cells and tissues was measured. Its roles in proliferation and expression of interleukins (ILs) were investigated by use of its specific siRNA or inhibitor (verteporfin, VP).ResultsYAP was upregulated in endometrial cancer cells and tissues. Knockdown of YAP or VP can suppress the proliferation while increase its chemo-sensitivity of EC cells. We found that targeted inhibition of YAP can decrease the expression of interleukin-6 (IL-6) and IL-11 in EC cells. Recombinant IL-6 or IL-11 can attenuate si-YAP suppressed proliferation of EC cells. Chromatin immunoprecipitation (ChIP) assay suggested that YAP can directly bind with the promoter of IL-6 and induce its transcription. As to IL-11, inhibitor of NF-κB (BAY 11–7082) can significantly down regulate the mRNA expression of IL-11. Over expression of p65 abolished si-YAP suppressed transcription of IL-11. It suggested that NF-κB was involved in the YAP regulated expression of IL-11.ConclusionsYAP can regulate the proliferation and progression of EC cells. It suggested that targeted inhibition of YAP might be a potent potential approach for EC therapy.

中文翻译：

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YAP通过调节IL-6和IL-11促进子宫内膜癌细胞恶性

背景新出现的证据表明，Hippo 信号通路可以调节各种癌症的进展。而Hippo信号的关键转导蛋白Yes相关蛋白(YAP)在子宫内膜癌(EC)发生发展中的作用却鲜有研究。方法检测YAP在子宫内膜癌细胞和组织中的表达。利用其特异性siRNA或抑制剂（维替泊芬，VP）研究其在增殖和白细胞介素（ILs）表达中的作用。结果YAP在子宫内膜癌细胞和组织中表达上调。敲低YAP或VP可以抑制EC细胞的增殖，同时增加其化疗敏感性。我们发现靶向抑制 YAP 可以降低 EC 细胞中白细胞介素 6 (IL-6) 和 IL-11 的表达。重组IL-6或IL-11可以减弱si-YAP抑制的EC细胞增殖。染色质免疫沉淀（ChIP）分析表明YAP可以直接与IL-6的启动子结合并诱导其转录。对于IL-11，NF-κB抑制剂(BAY 11-7082)可以显着下调IL-11 mRNA的表达。p65 的过度表达消除了 si-YAP 对 IL-11 转录的抑制。提示NF-κB参与YAP调节IL-11的表达。结论YAP可以调节EC细胞的增殖和进展。这表明 YAP 的靶向抑制可能是 EC 治疗的一种有效的潜在方法。