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Open Access Highly Accessed Research article

Special role of Foxp3 for the specifically altered microRNAs in Regulatory T cells of HCC patients

Long Chen1, Huiying Ma1, Heng Hu1, Lingling Gao1, Xuan Wang1, Jiaqi Ma1, Qiang Gao2, Binbin Liu2, Guomin Zhou1 and Chunmin Liang12*

Author Affiliations

1 Lab of Tumor Immunology, Department of Anatomy and Histology & Embryology, Shanghai Medical College of Fudan University, 138 Yixueyuan Road, 200032 Shanghai, PR China

2 Liver Cancer Institute, Zhongshan Hospital, Shanghai Medical College; Key laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, 136 Yixueyuan Road, 200032 Shanghai, PR China

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BMC Cancer 2014, 14:489  doi:10.1186/1471-2407-14-489

Published: 7 July 2014

Abstract

Background

Regulatory T cells (Tregs) exhibit functional abnormalities in the context of hepatocellular carcinoma (HCC). The microRNAs (miRNAs) are identified as the key modulators in Tregs. This study was to explore whether the expression profiles of miRNAs of Tregs were different in HCC-activated Tregs and whether Foxp3 had special effects on them.

Methods

We isolated HCC-activated Tregs from mice bearing HCC and compared the expression profiles of miRNAs between HCC-activated Tregs and control Tregs by microarray. RNA interference against Foxp3 was also performed through transfection of synthetic siRNAs to Tregs for analyzing the effect of Foxp3 on the expression of miRNAs. Tregs isolated from HCC patients (nā€‰=ā€‰12) and healthy controls (nā€‰=ā€‰7) were used for validation of the differentially expressed miRNAs. Finally, bioinformatic analysis was applied to infer their possible roles.

Results

We found nine specifically altered miRNAs in HCC-activated Tregs from the murine model. After transfection with siRNAs against Foxp3, control Tregs showed obvious reduction of Foxp3 and five miRNAs were significantly changed; HCC-activated Tregs exhibited a slight reduction of Foxp3 with three miRNAs significantly changed. Tregs from HCC patients and healthy controls finally confirmed the up-regulation of four miRNAs (hsa-miR-182-5p, hsa-miR-214-3p, hsa-miR-129-5p and hsa-miR-30b-5p). Following bioinformatic analysis suggested these altered miRNAs would target eight important signaling pathways that could affect the functions of Tregs.

Conclusions

Our studies provided the first evidence that Tregs in HCC had the specifically altered expression of miRNAs, which was affected by Foxp3. These results are useful both in finding new biomarkers and in further exploring the functions of Tregs in HCC patients.

Keywords:
Regulatory T cells; Hepatocellular carcinoma; microRNAs array; Foxp3 RNA interference; Bioinformatics