YAP-1 Promotes Tregs Differentiation in Hepatocellular Carcinoma by Enhancing TGFBR2 Transcription
YAP-1 Promotes Tregs Differentiation in Hepatocellular Carcinoma by Enhancing TGFBR2 Transcription
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DOI：
10.1159/000464380
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发表时间：
2017-01-01
影响因子：
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通讯作者：
Zhang, Chuanyong
中科院分区：
文献类型：
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作者：
Fan, Ye;Gao, Yangjuan;Zhang, Chuanyong
背景/目的：免疫抑制是癌症的标志之一；然而，其分子机制仍不清楚。在本研究中，我们试图研究 yes 相关蛋白 1 (YAP-1) 的表达和激活及其在肝细胞癌 (HCC) 内 T 细胞中的作用。方法：通过实时PCR、免疫组化染色、蛋白质印迹和流式细胞术检测YAP-1的表达和激活。使用生物信息学工具预测 YAP-1 对调节性 T 细胞 (Treg) 分化的潜在调节作用，并通过体外研究进行验证。结果：外周血单个核细胞中检测到YAP-1的显着过度表达和激活，并与Treg百分比呈正线性相关；它可以作为不良预后的一个有价值的指标。通过体外研究，我们发现 YAP-1 的过表达和激活可以通过增加 TGFBR2 的表达来促进幼稚 T 细胞对 Tregs 的极化刺激。 YAP-1/TEADs DNA 结合位点位于 TGFBR2 的启动子区域内，与其转录活性相关。 YAP-1 通过 TEAD 直接与 TGFBR2 启动子结合，充当 TGFBR2 转录的共激活剂。结论：HCC T细胞中YAP-1的过表达和激活可以通过TGFBR2转录增强促进Treg分化而诱导免疫抑制。 (C) 2017 作者
Background/Aims: Immunosuppression is one of the hallmarks of cancer; however, its molecular mechanism remains unknown. In the present study, we sought to investigate the expression and activation of yes-associated protein 1 (YAP-1) and its roles in T cells within hepatocellular carcinoma (HCC). Methods: The expression and activation of YAP-1 were accessed by real-time PCR, immunohistochemistry staining, western blot, and flow cytometry. The potential regulation effect of YAP-1 on Regulatory T cells (Tregs) differentiation was predicted using bioinformatics tools and verified by in vitro studies. Results: Significant overexpression and activation of YAP-1 was detected within peripheral blood mononuclear cells and showed positive linear correlation to Treg percentage; it may serve as a valuable indicator of a bad prognosis. Using in vitro studies, we found that overexpression and activation of YAP-1 can promote naive T cell polarization stimulation to Tregs by increasing the expression of TGFBR2. The YAP-1/TEADs DNA binding site was spotted within the promoter region of TGFBR2 and related to its transcription activity. YAP-1 acted as a co-activator of TGFBR2 transcription by binding directly to the TGFBR2 promoter through TEADs. Conclusion: Overexpression and activation of YAP-1 in HCC T cells can induce immunosuppression by promoting Treg differentiation via transcriptional enhancement of TGFBR2. (C) 2017 The Author(s)