TGF-β1 Promotes Colorectal Cancer Immune Escape by Elevating B7-H3 and B7-H4 Via the MiR-155/miR-143 Axis

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Sep 15

PMID 27626488

Citations 41

Authors

Xinru Zhou

Yong Mao

Jianjie Zhu

Fanyi Meng

Qi Chen

Lihua Tao

Rui Li

Fengqing Fu

Cuiping Liu

Yuanjia Hu

Weipeng Wang

Hongjian Zhang

Dong Hua

Weichang Chen

Xueguang Zhang

Affiliations

Soon will be listed here.

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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