Department of Clinical Laboratory, Kunshan First People's Hospital, Affiliated To Jiangsu University, Kunshan, 215300, People's Republic of China.
Department of Gastroenterology, Zhenjiang Hospital Affiliated to Nanjing University of Chinese Medicine, Zhenjiang, 212000, People's Republic of China.
Gastric Cancer. 2021 Jan;24(1):85-102. doi: 10.1007/s10120-020-01099-9. Epub 2020 Jul 4.
YAP1 is a core protein of the Hippo signaling pathway and is associated with malignancy and immunosuppression. In the present study, we discovered a novel lncRNA, RP11-323N12.5, with tumor promotion and immunosuppression activities through enhancing transcription of YAP1.
RP11-323N12.5 was identified using GEPIA. Its expression levels and their relationship with clinical features were investigated using clinical samples. The regulation of YAP1 transcription by RP11-323N12.5 was investigated in both GC and T cells, the tumor and immunosuppression promotion roles of RP11-323N12.5 were explored in vitro and in vivo.
RP11-323N12.5 was the most up-regulated lncRNA in human GC, based on data from the TCGA database. Its transcription was significantly positively correlated with YAP1 transcription, YAP1 downstream gene expression which contribute to tumor growth and immunosuppression. RP11-323N12.5 promoted YAP1 transcription by binding to c-MYC in the YAP1 promoter region. Meanwhile, transcription of RP11-323N12.5 was also regulated by YAP1/TAZ/TEADs activation in GC cells. RP11-323N12.5 had tumor- and immnosuppression-promoting effects by enhancing YAP1 downstream genes in GC cells. Excessive RP11-323N12.5 was also observed in tumor-infiltrating leukocytes (TILs), which may be exosome-derived and also be related to enhanced Treg differentiation as a result YAP1 up-regulation. Moreover, RP11-323N12.5 promoted tumor growth and immunosuppression via YAP1 up-regulation in vivo.
RP11-323N12.5 was the most up-regulated lncRNA in human GC and it promoted YAP1 transcription by binding to c-MYC within the YAP1 promoter in both GC and T cells. RP11-323N12.5 is an ideal therapeutic target in human GC due to its tumor-promoting and immunosuppression characteristics.
YAP1 是 Hippo 信号通路的核心蛋白，与恶性肿瘤和免疫抑制有关。本研究发现了一种新的长链非编码 RNA（lncRNA）RP11-323N12.5，它通过增强 YAP1 的转录来促进肿瘤发生和免疫抑制。
使用 GEPIA 鉴定 RP11-323N12.5。使用临床样本研究其表达水平及其与临床特征的关系。在 GC 和 T 细胞中研究 RP11-323N12.5 对 YAP1 转录的调控，在体外和体内研究 RP11-323N12.5 对肿瘤和免疫抑制的促进作用。
根据 TCGA 数据库的数据，RP11-323N12.5 是人类 GC 中上调最明显的 lncRNA。其转录与 YAP1 转录、YAP1 下游促进肿瘤生长和免疫抑制的基因表达呈显著正相关。RP11-323N12.5 通过结合 YAP1 启动子区域的 c-MYC 促进 YAP1 转录。同时，GC 细胞中 YAP1/TAZ/TEADs 的激活也调节 RP11-323N12.5 的转录。RP11-323N12.5 通过增强 GC 细胞中 YAP1 下游基因促进肿瘤发生和免疫抑制。在肿瘤浸润性白细胞（TILs）中也观察到过多的 RP11-323N12.5，这可能是外泌体衍生的，也与 YAP1 上调导致的 Treg 分化增强有关。此外，RP11-323N12.5 通过体内 YAP1 上调促进肿瘤生长和免疫抑制。
RP11-323N12.5 是人类 GC 中上调最明显的 lncRNA，它通过结合 YAP1 启动子区域的 c-MYC 在 GC 和 T 细胞中促进 YAP1 转录。RP11-323N12.5 具有促进肿瘤发生和免疫抑制的特性，是人类 GC 的理想治疗靶点。
