Cell-free miR-17-5p as a diagnostic biomarker for gastric cancer inhibits dendritic cell maturation
Zi-Jin Cui,1,2 Xiao-Li Xie,1 Wei Qi,1 Yi-Chao Yang,1 Yun Bai,2 Jing Han,1 Qian Ding,1 Hui-Qing Jiang1 1Department of Gastroenterology, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Rep...
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doaj-255916caf9a04ea5877eb5fdcffe36992020-11-25T01:22:19ZengDove Medical PressOncoTargets and Therapy1178-69302019-04-01Volume 122661267544995Cell-free miR-17-5p as a diagnostic biomarker for gastric cancer inhibits dendritic cell maturationCui ZJXie XLQi WYang YCBai YHan JDing QJiang HQZi-Jin Cui,1,2 Xiao-Li Xie,1 Wei Qi,1 Yi-Chao Yang,1 Yun Bai,2 Jing Han,1 Qian Ding,1 Hui-Qing Jiang1 1Department of Gastroenterology, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Gastroenterology, Hebei General Hospital, Shijiazhuang, People’s Republic of China Purpose: Gastric cancer (GC) patients display aberrant miRNA expression and defective dendritic cell function. However, the role of cancer cell-derived oncomiR in GC detection and dendritic cell (DC) maturation remains largely elusive. Methods: Candidate miRNAs were selected by deep sequencing (8 GC plasma samples vs 8 control plasma samples; 8 GC tissues vs 8 adjacent normal gastric tissues) and confirmed by PCR with 164 plasma samples and 72 formalin-fixed paraffin-embedded GC tissue samples. Their diagnostic performance was evaluated by receiver operating characteristic curve. Cy3 fluorescence signals in DCs, exposed to conditioned medium obtained from BGC-823 cells pre-transfected with Cy3-miR-17-5p, were determined by flow cytometry and visualized by confocal microscopy. Functional and phenotypical alterations of DCs were assayed when DCs were transfected with miR-17-5p in vitro. Results: Deep sequencing and RT-PCR confirmed that five shared miRNAs were upregulated in plasma and tissue samples of GC patients. Cell-free miR-17-5p was superior to others in GC detection with an area under the curve of 0.82, and correlated with lymphatic metastasis and poor overall survival. GC cell-shuttled miR-17-5p can be delivered to immature DCs, and they significantly inhibited LPS-stimulated phenotypic maturation by diminishing the expression of maturation markers (MHC II, CD80 and CD86 molecules). In line with those alterations in the phenotypic markers, functional experiments demonstrated that miR-17-5p triggered an inhibitory effect on DCs endocytic activity and decreased tumor necrosis factor-α and IL-12 secretion, while enhancing IL-10 production. Mixed lymphocyte reaction showed that miR-17-5p inhibited the T cell stimulating effect of DCs and favored regulatory T cells expansion. Conclusion: GC cell-derived miR-17-5p is a potential biomarker for GC detection. Taken up by DCs, miR-17-5p weakened antitumor immune responses via inhibiting the maturation of dendritic cells. Keywords: gastric cancer, cell-free miRNA, biomarker, intracellular communication, dendritic cellhttps://www.dovepress.com/cell-free-mir-17-5p-as-a-diagnostic-biomarker-for-gastric-cancer-inhib-peer-reviewed-article-OTTgastric cancercell-free miRNAbiomarkerintracellular communicationdendritic cell. |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Cui ZJ Xie XL Qi W Yang YC Bai Y Han J Ding Q Jiang HQ |
spellingShingle |
Cui ZJ Xie XL Qi W Yang YC Bai Y Han J Ding Q Jiang HQ Cell-free miR-17-5p as a diagnostic biomarker for gastric cancer inhibits dendritic cell maturation OncoTargets and Therapy gastric cancer cell-free miRNA biomarker intracellular communication dendritic cell. |
author_facet |
Cui ZJ Xie XL Qi W Yang YC Bai Y Han J Ding Q Jiang HQ |
author_sort |
Cui ZJ |
title |
Cell-free miR-17-5p as a diagnostic biomarker for gastric cancer inhibits dendritic cell maturation |
title_short |
Cell-free miR-17-5p as a diagnostic biomarker for gastric cancer inhibits dendritic cell maturation |
title_full |
Cell-free miR-17-5p as a diagnostic biomarker for gastric cancer inhibits dendritic cell maturation |
title_fullStr |
Cell-free miR-17-5p as a diagnostic biomarker for gastric cancer inhibits dendritic cell maturation |
title_full_unstemmed |
Cell-free miR-17-5p as a diagnostic biomarker for gastric cancer inhibits dendritic cell maturation |
title_sort |
cell-free mir-17-5p as a diagnostic biomarker for gastric cancer inhibits dendritic cell maturation |
publisher |
Dove Medical Press |
series |
OncoTargets and Therapy |
issn |
1178-6930 |
publishDate |
2019-04-01 |
description |
Zi-Jin Cui,1,2 Xiao-Li Xie,1 Wei Qi,1 Yi-Chao Yang,1 Yun Bai,2 Jing Han,1 Qian Ding,1 Hui-Qing Jiang1 1Department of Gastroenterology, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Gastroenterology, Hebei General Hospital, Shijiazhuang, People’s Republic of China Purpose: Gastric cancer (GC) patients display aberrant miRNA expression and defective dendritic cell function. However, the role of cancer cell-derived oncomiR in GC detection and dendritic cell (DC) maturation remains largely elusive. Methods: Candidate miRNAs were selected by deep sequencing (8 GC plasma samples vs 8 control plasma samples; 8 GC tissues vs 8 adjacent normal gastric tissues) and confirmed by PCR with 164 plasma samples and 72 formalin-fixed paraffin-embedded GC tissue samples. Their diagnostic performance was evaluated by receiver operating characteristic curve. Cy3 fluorescence signals in DCs, exposed to conditioned medium obtained from BGC-823 cells pre-transfected with Cy3-miR-17-5p, were determined by flow cytometry and visualized by confocal microscopy. Functional and phenotypical alterations of DCs were assayed when DCs were transfected with miR-17-5p in vitro. Results: Deep sequencing and RT-PCR confirmed that five shared miRNAs were upregulated in plasma and tissue samples of GC patients. Cell-free miR-17-5p was superior to others in GC detection with an area under the curve of 0.82, and correlated with lymphatic metastasis and poor overall survival. GC cell-shuttled miR-17-5p can be delivered to immature DCs, and they significantly inhibited LPS-stimulated phenotypic maturation by diminishing the expression of maturation markers (MHC II, CD80 and CD86 molecules). In line with those alterations in the phenotypic markers, functional experiments demonstrated that miR-17-5p triggered an inhibitory effect on DCs endocytic activity and decreased tumor necrosis factor-α and IL-12 secretion, while enhancing IL-10 production. Mixed lymphocyte reaction showed that miR-17-5p inhibited the T cell stimulating effect of DCs and favored regulatory T cells expansion. Conclusion: GC cell-derived miR-17-5p is a potential biomarker for GC detection. Taken up by DCs, miR-17-5p weakened antitumor immune responses via inhibiting the maturation of dendritic cells. Keywords: gastric cancer, cell-free miRNA, biomarker, intracellular communication, dendritic cell |
topic |
gastric cancer cell-free miRNA biomarker intracellular communication dendritic cell. |
url |
https://www.dovepress.com/cell-free-mir-17-5p-as-a-diagnostic-biomarker-for-gastric-cancer-inhib-peer-reviewed-article-OTT |
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