期刊
ONCOTARGET
卷 7, 期 41, 页码 67196-67211出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.11950
关键词
colorectal cancer; tumor evasion; TGF-beta 1; co-inhibitor; microRNA
资金
- National Natural Science Foundation of China [81270031, 81272737, 81372375, 81473278]
- Science and Technology Special Project of Clinical Medicine in Jiangsu Province [BL2014046]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
Transforming growth factor-beta 1 (TGF-beta 1) suppresses T cell function, promoting tumor immune escape. Yet, whether the depression of TGF-beta 1 on T cell function is mediated by co-inhibitory molecules B7-H3 and B7-H4 remains largely unclear. Here, we demonstrated that TGF-beta 1 elevated the expression of miR-155 in colorectal cancer cells through SMAD3 and SMAD4. The upregulated miR-155 attenuated miR-143 by inhibiting its direct target, the transcription factor CEBPB. Consequently, the direct target genes of miR-143, B7-H3 and B7-H4, were augmented in the cytoplasm and membrane of tumor cells. Over-expression of B7-H3 and B7-H4 in HCT-116 cells induced T cells to secrete TGF-beta 1 and the immunosuppressive cytokines IL-2, IL-6, and IL-17. Restoration of miR-143 inhibited the growth of HCT-116 xenograft tumors in mice, and also repressed the expression of B7-H3 and B7-H4 in the tumors. Thus, this study reveals the mechanism by which TGF-beta 1 leads to T cell-mediated tumor evasion through an increase in B7-H3 and B7-H4 expression.
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