[HTML][HTML] TGF-β1 promotes colorectal cancer immune escape by elevating B7-H3 and B7-H4 via the miR-155/miR-143 axis

X Zhou, Y Mao, J Zhu, F Meng, Q Chen, L Tao, R Li… - Oncotarget, 2016 - ncbi.nlm.nih.gov
X Zhou, Y Mao, J Zhu, F Meng, Q Chen, L Tao, R Li, F Fu, C Liu, Y Hu, W Wang, H Zhang…
Oncotarget, 2016ncbi.nlm.nih.gov
Transforming growth factor-beta 1 (TGF-β1) suppresses T cell function, promoting tumor
immune escape. Yet, whether the depression of TGF-β1 on T cell function is mediated by co-
inhibitory molecules B7-H3 and B7-H4 remains largely unclear. Here, we demonstrated that
TGF-β1 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 …
Abstract
Transforming growth factor-beta 1 (TGF-β1) suppresses T cell function, promoting tumor immune escape. Yet, whether the depression of TGF-β1 on T cell function is mediated by co-inhibitory molecules B7-H3 and B7-H4 remains largely unclear. Here, we demonstrated that TGF-β1 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-β1 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-β1 leads to T cell-mediated tumor evasion through an increase in B7-H3 and B7-H4 expression.
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