YAP-1 Promotes Tregs Differentiation in Hepatocellular Carcinoma by Enhancing TGFBR2 Transcription.

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). 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. 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 naïve 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. Overexpression and activation of YAP-1 in HCC T cells can induce immunosuppression by promoting Treg differentiation via transcriptional enhancement of TGFBR2. © 2017 The Author(s). Published by S. Karger AG, Basel.

Citation

Ye Fan, Yangjuan Gao, Jianhua Rao, Ke Wang, Feng Zhang, Chuanyong Zhang. YAP-1 Promotes Tregs Differentiation in Hepatocellular Carcinoma by Enhancing TGFBR2 Transcription. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2017;41(3):1189-1198

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PMID: 28472799

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