长链非编码 RNA lnc-EGFR 刺激调节性 T 细胞分化，从而促进肝癌的免疫逃逸。
The long noncoding RNA lnc-EGFR stimulates T-regulatory cells differentiation thus promoting hepatocellular carcinoma immune evasion.
机构信息
Liver Transplantation Center of the First Affiliated Hospital and Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu Province 210029, P.R. China.
Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, P.R. China.
出版信息
Nat Commun. 2017 May 25;8:15129. doi: 10.1038/ncomms15129.
Long noncoding RNAs play a pivotal role in T-helper cell development but little is known about their roles in Treg differentiation and functions during the progression of hepatocellular carcinoma (HCC). Here, we show that lnc-epidermal growth factor receptor (EGFR) upregulation in Tregs correlates positively with the tumour size and expression of EGFR/Foxp3, but negatively with IFN-γ expression in patients and xenografted mouse models. Lnc-EGFR stimulates Treg differentiation, suppresses CTL activity and promotes HCC growth in an EGFR-dependent manner. Mechanistically, lnc-EGFR specifically binds to EGFR and blocks its interaction with and ubiquitination by c-CBL, stabilizing it and augmenting activation of itself and its downstream AP-1/NF-AT1 axis, which in turn elicits EGFR expression. Lnc-EGFR links an immunosuppressive state to cancer by promoting Treg cell differentiation, thus offering a potential therapeutic target for HCC.
长非编码 RNA 在辅助性 T 细胞发育中发挥关键作用，但它们在调节性 T 细胞分化及其在肝细胞癌（HCC）进展中的功能方面的作用知之甚少。在这里，我们显示 Treg 中 lnc-表皮生长因子受体（EGFR）的上调与肿瘤大小以及患者和异种移植小鼠模型中 EGFR/Foxp3 的表达呈正相关，但与 IFN-γ 的表达呈负相关。Lnc-EGFR 以 EGFR 依赖的方式刺激 Treg 分化、抑制 CTL 活性并促进 HCC 生长。在机制上，lnc-EGFR 特异性结合 EGFR，并阻止其与 c-CBL 的相互作用及其泛素化，从而稳定 EGFR 并增强其自身及其下游 AP-1/NF-AT1 轴的激活，进而引发 EGFR 表达。Lnc-EGFR 通过促进 Treg 细胞分化将免疫抑制状态与癌症联系起来，因此为 HCC 提供了一个潜在的治疗靶点。
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