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BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

FOXP3 Is a HCC suppressor gene and Acts through regulating the TGF-β/Smad2/3 signaling pathway

Authors: Jie-Yi Shi, Li-Jie Ma, Ji-Wei Zhang, Meng Duan, Zhen-Bin Ding, Liu-Xiao Yang, Ya Cao, Jian Zhou, Jia Fan, Xiaoming Zhang, Ying-Jun Zhao, Xiao-Ying Wang, Qiang Gao

Published in: BMC Cancer | Issue 1/2017

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Abstract

Background

FOXP3 has been discovered to be expressed in tumor cells and participate in the regulation of tumor behavior. Herein, we investigated the clinical relevance and biological significance of FOXP3 expression in human hepatocellular carcinoma (HCC).

Methods

Expression profile of FOXP3 was analyzed using real-time RT-PCR, western blotting and immunofluorescence on HCC cell lines, and immunostaing of a tissue microarray containing of 240 primary HCC samples. The potential regulatory roles of FOXP3 were dissected by an integrated approach, combining biochemical assays, analysis of patient survival, genetic manipulation of HCC cell lines, mouse xenograft tumor models and chromatin immunoprecipitation (ChIP) sequencing.

Results

FOXP3 was constitutively expressed in HCC cells with the existence of splice variants (especially exon 3 and 4 deleted, Δ3,4-FOXP3). High expression of FOXP3 significantly correlated with low serum α-fetoprotein (AFP) level, absence of vascular invasion and early TNM stage. Survival analyses revealed that increased FOXP3 expression was significantly associated with better survival and reduced recurrence, and served as an independent prognosticator for HCC patients. Furthermore, FOXP3 could potently suppress the proliferation and invasion of HCC cells in vitro and reduce tumor growth in vivo. However, Δ3,4-FOXP3 showed a significant reduction in the tumor-inhibiting effect. The inhibition of FOXP3 on HCC aggressiveness was acted probably by enhancing the TGF-β/Smad2/3 signaling pathway.

Conclusion

Our findings suggest that FOXP3 suppresses tumor progression in HCC via TGF-β/Smad2/3 signaling pathway, highlighting the role of FOXP3 as a prognostic factor and novel target for an optimal therapy against this fatal malignancy.
Appendix
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Metadata
Title
FOXP3 Is a HCC suppressor gene and Acts through regulating the TGF-β/Smad2/3 signaling pathway
Authors
Jie-Yi Shi
Li-Jie Ma
Ji-Wei Zhang
Meng Duan
Zhen-Bin Ding
Liu-Xiao Yang
Ya Cao
Jian Zhou
Jia Fan
Xiaoming Zhang
Ying-Jun Zhao
Xiao-Ying Wang
Qiang Gao
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3633-6

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