Special role of Foxp3 for the specifically altered microRNAs in Regulatory T cells of HCC patientsReportar como inadecuado




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BMC Cancer

, 14:489

Infection, immunity and cancer vaccines

Abstract

BackgroundRegulatory 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.

MethodsWe 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 n = 12 and healthy controls n = 7 were used for validation of the differentially expressed miRNAs. Finally, bioinformatic analysis was applied to infer their possible roles.

ResultsWe 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.

ConclusionsOur 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.

KeywordsRegulatory T cells Hepatocellular carcinoma microRNAs array Foxp3 RNA interference Bioinformatics AbbreviationsHCCHepatocellular carcinoma

TregsRegulatory T cells

miRNAsmicroRNAs

RNAiRNA interference

MFIMean fluorescence intensity

FACSFluorescence-activated cell sorting.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-14-489 contains supplementary material, which is available to authorized users.

Long Chen, Huiying Ma, Heng Hu contributed equally to this work.

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Autor: Long Chen - Huiying Ma - Heng Hu - Lingling Gao - Xuan Wang - Jiaqi Ma - Qiang Gao - Binbin Liu - Guomin Zhou - Chunmin 

Fuente: https://link.springer.com/







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