RP11-323N12.5 promotes the malignancy and immunosuppression of human gastric cancer by increasing YAP1 transcription

Background 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. Methods RP11-323N12.5was identified using GEPIA. Its expression levels and their relationship with clinical features were investigated using clinical samples. The regulation of YAP1 transcription byRP11-323N12.5was investigated in both GC and T cells, the tumor and immunosuppression promotion roles ofRP11-323N12.5were explored in vitroand in vivo. Results RP11-323N12.5was 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.RP11-323N12.5promoted YAP1 transcription by binding to c-MYC in theYAP1promoter region. Meanwhile, transcription ofRP11-323N12.5was also regulated by YAP1/TAZ/TEADs activation in GC cells.RP11-323N12.5had tumor- and immnosuppression-promoting effects by enhancing YAP1 downstream genes in GC cells. ExcessiveRP11-323N12.5was also observed in tumor-infiltrating leukocytes (TILs), which may be exosome-derived and also be related to enhanced Treg differentiation as a resultYAP1up-regulation. Moreover,RP11-323N12.5promoted tumor growth and immunosuppression via YAP1 up-regulation in vivo. Conclusions RP11-323N12.5was the most up-regulated lncRNA in human GC and it promotedYAP1transcription by binding to c-MYC within theYAP1promoter in both GC and T cells.RP11-323N12.5is an ideal therapeutic target in human GC due to its tumor-promoting and immunosuppression characteristics.