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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
Xinru Zhou1; Yong Mao2; Jianjie Zhu1; Fanyi Meng1; Qi Chen1; Lihua Tao3; Rui Li3; Fengqing Fu4; Cuiping Liu4; Yuanjia Hu5; Weipeng Wang1; Hongjian Zhang1; Dong Hua2; Weichang Chen3; Xueguang Zhang4
2016
Source PublicationOncotarget
ISSN19492553
Volume7Issue:41Pages:67196-67211
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 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
Indexed BySCIE
Language英语
WOS Research AreaOncology ; Cell Biology
WOS SubjectOncology ; Cell Biology
WOS IDWOS:000387446200067
The Source to ArticleScopus
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Cited Times [WOS]:37   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorWeipeng Wang
Affiliation1.Center for Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou, China
2.Department of Oncology, The Fourth Affiliated Hospital of Soochow University, Wuxi, China
3.Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
4.Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, China
5.Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, China
Recommended Citation
GB/T 7714
Xinru Zhou,Yong Mao,Jianjie Zhu,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):67196-67211.
APA Xinru Zhou.,Yong Mao.,Jianjie Zhu.,Fanyi Meng.,Qi Chen.,...&Xueguang Zhang.(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),67196-67211.
MLA Xinru Zhou,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):67196-67211.
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