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TGF-β1 promotes colorectal cancer immune escape by elevating B7-H3 and B7-H4 via the miR-155/miR-143 axis
Zhou X.; Mao Y.; Zhu J.; Meng F.; Chen Q.; Tao L.; Li R.; Fu F.; Liu C.; Hu Y.; Wang W.; Zhang H.; Hua D.; Chen W.; Zhang X.
2016
Source PublicationOncotarget
ISSN19492553
Volume7Issue:41Pages:67196
AbstractTransforming 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 cellmediated tumor evasion through an increase in B7-H3 and B7-H4 expression.
KeywordCo-inhibitor Colorectal cancer MicroRNA TGF-β1 Tumor evasion
DOI10.18632/oncotarget.11950
URLView the original
Language英语
The Source to ArticleScopus
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Cited Times [WOS]:28   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Recommended Citation
GB/T 7714
Zhou X.,Mao Y.,Zhu J.,et al. TGF-β1 promotes colorectal cancer immune escape by elevating B7-H3 and B7-H4 via the miR-155/miR-143 axis[J]. Oncotarget,2016,7(41):67196.
APA Zhou X..,Mao Y..,Zhu J..,Meng F..,Chen Q..,...&Zhang X..(2016).TGF-β1 promotes colorectal cancer immune escape by elevating B7-H3 and B7-H4 via the miR-155/miR-143 axis.Oncotarget,7(41),67196.
MLA Zhou X.,et al."TGF-β1 promotes colorectal cancer immune escape by elevating B7-H3 and B7-H4 via the miR-155/miR-143 axis".Oncotarget 7.41(2016):67196.
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