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MicroRNA-22 impairs anti-tumor ability of dendritic cells by targeting p38.

Liang X, Liu Y, Mei S, Zhang M, Xin J, Zhang Y, Yang R - PLoS ONE (2015)

Bottom Line: Dendritic cells (DCs) play a critical role in triggering anti-tumor immune responses.In this study, we identified microRNA-22 (miR-22) as a microRNA inhibiting p38 protein expression by directly binding to the 3' untranslated region (3'UTR) of its mRNA.The p38 down-regulation further interfered with the synthesis of DC-derived IL-6 and the differentiation of DC-driven Th17 cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Nankai University School of Medicine, Tianjin, China; Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China.

ABSTRACT
Dendritic cells (DCs) play a critical role in triggering anti-tumor immune responses. Their intracellular p38 signaling is of great importance in controlling DC activity. In this study, we identified microRNA-22 (miR-22) as a microRNA inhibiting p38 protein expression by directly binding to the 3' untranslated region (3'UTR) of its mRNA. The p38 down-regulation further interfered with the synthesis of DC-derived IL-6 and the differentiation of DC-driven Th17 cells. Moreover, overexpression of miR-22 in DCs impaired their tumor-suppressing ability while miR-22 inhibitor could reverse this phenomenon and improve the curative effect of DC-based immunotherapy. Thus, our results highlight a suppressive role for miR-22 in the process of DC-invoked anti-tumor immunity and that blocking this microRNA provides a new strategy for generating potent DC vaccines for patients with cancer.

No MeSH data available.


Related in: MedlinePlus

miR-22 inhibitor enhances the anti-tumor ability of DCs.The curative effects of the immunotherapy using differentially treated DCs were evaluated in 4 aspects including tumor growth plot (A), final tumor volume (B), animal survival time (C) and final tumor weight (D). The miR-22 mimics treated DC group showed the weakest therapeutic results. Except for the untreated group, it had the fastest tumor growth rate, the largest tumor volume, the shortest animal survival time and the heaviest tumor weight. On the other hand, the miR-22 inhibitor transfected DCs had the strongest interference on tumor development. The original effect of negative control DCs was enhanced when miR-22 inhibitor was added. These results suggested the tumor-suppressing function of miR-22 inhibitor. All the groups involved in this figure contained 5 mice receiving the indicated treatment. The mice in untreated group were injected intratumorally with PBS instead of DCs, while the other 3 groups were injected with DCs transfected with miR-22 mimics, miR-22 inhibtor and negative control oligonucleotide respectively. The plots of (A) and (D) are expressed as mean±SD.
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pone.0121510.g005: miR-22 inhibitor enhances the anti-tumor ability of DCs.The curative effects of the immunotherapy using differentially treated DCs were evaluated in 4 aspects including tumor growth plot (A), final tumor volume (B), animal survival time (C) and final tumor weight (D). The miR-22 mimics treated DC group showed the weakest therapeutic results. Except for the untreated group, it had the fastest tumor growth rate, the largest tumor volume, the shortest animal survival time and the heaviest tumor weight. On the other hand, the miR-22 inhibitor transfected DCs had the strongest interference on tumor development. The original effect of negative control DCs was enhanced when miR-22 inhibitor was added. These results suggested the tumor-suppressing function of miR-22 inhibitor. All the groups involved in this figure contained 5 mice receiving the indicated treatment. The mice in untreated group were injected intratumorally with PBS instead of DCs, while the other 3 groups were injected with DCs transfected with miR-22 mimics, miR-22 inhibtor and negative control oligonucleotide respectively. The plots of (A) and (D) are expressed as mean±SD.

Mentions: The original purpose of our study was to find microRNAs with the ability to suppress the p38 gene and develop a feasible tumor therapy strategy by virtue of these RNAs. Hence, the curative effect of miR-22 related oligonucleotides bearing DCs on the B16 mice tumor model was our central focus. The experimental results showed that miR-22 exhibited a tumor promoting effect and impaired the effectiveness of immunotherapy. The mice of miR-22 mimics group had the fastest rate of tumor development (Fig 5A), the largest size of tumor (Fig 5B), the shortest survival time (Fig 5C) and the heaviest tumor weight (Fig 5D) in all the DC treated groups. In contrast, the curative effect of the miR-22 inhibitor group was the strongest of all (Fig 5). The original effect of negative control DCs was enhanced when miR-22 inhibitor was added. These results prompted us to make a conclusion that in DCs, miR-22 could suppress p38 gene expression and further impair the ability of DCs to interfere with the tumor growth, while miR-22 inhibitor could invert this effect and act as a potential immunotherapy reagent.


MicroRNA-22 impairs anti-tumor ability of dendritic cells by targeting p38.

Liang X, Liu Y, Mei S, Zhang M, Xin J, Zhang Y, Yang R - PLoS ONE (2015)

miR-22 inhibitor enhances the anti-tumor ability of DCs.The curative effects of the immunotherapy using differentially treated DCs were evaluated in 4 aspects including tumor growth plot (A), final tumor volume (B), animal survival time (C) and final tumor weight (D). The miR-22 mimics treated DC group showed the weakest therapeutic results. Except for the untreated group, it had the fastest tumor growth rate, the largest tumor volume, the shortest animal survival time and the heaviest tumor weight. On the other hand, the miR-22 inhibitor transfected DCs had the strongest interference on tumor development. The original effect of negative control DCs was enhanced when miR-22 inhibitor was added. These results suggested the tumor-suppressing function of miR-22 inhibitor. All the groups involved in this figure contained 5 mice receiving the indicated treatment. The mice in untreated group were injected intratumorally with PBS instead of DCs, while the other 3 groups were injected with DCs transfected with miR-22 mimics, miR-22 inhibtor and negative control oligonucleotide respectively. The plots of (A) and (D) are expressed as mean±SD.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4380340&req=5

pone.0121510.g005: miR-22 inhibitor enhances the anti-tumor ability of DCs.The curative effects of the immunotherapy using differentially treated DCs were evaluated in 4 aspects including tumor growth plot (A), final tumor volume (B), animal survival time (C) and final tumor weight (D). The miR-22 mimics treated DC group showed the weakest therapeutic results. Except for the untreated group, it had the fastest tumor growth rate, the largest tumor volume, the shortest animal survival time and the heaviest tumor weight. On the other hand, the miR-22 inhibitor transfected DCs had the strongest interference on tumor development. The original effect of negative control DCs was enhanced when miR-22 inhibitor was added. These results suggested the tumor-suppressing function of miR-22 inhibitor. All the groups involved in this figure contained 5 mice receiving the indicated treatment. The mice in untreated group were injected intratumorally with PBS instead of DCs, while the other 3 groups were injected with DCs transfected with miR-22 mimics, miR-22 inhibtor and negative control oligonucleotide respectively. The plots of (A) and (D) are expressed as mean±SD.
Mentions: The original purpose of our study was to find microRNAs with the ability to suppress the p38 gene and develop a feasible tumor therapy strategy by virtue of these RNAs. Hence, the curative effect of miR-22 related oligonucleotides bearing DCs on the B16 mice tumor model was our central focus. The experimental results showed that miR-22 exhibited a tumor promoting effect and impaired the effectiveness of immunotherapy. The mice of miR-22 mimics group had the fastest rate of tumor development (Fig 5A), the largest size of tumor (Fig 5B), the shortest survival time (Fig 5C) and the heaviest tumor weight (Fig 5D) in all the DC treated groups. In contrast, the curative effect of the miR-22 inhibitor group was the strongest of all (Fig 5). The original effect of negative control DCs was enhanced when miR-22 inhibitor was added. These results prompted us to make a conclusion that in DCs, miR-22 could suppress p38 gene expression and further impair the ability of DCs to interfere with the tumor growth, while miR-22 inhibitor could invert this effect and act as a potential immunotherapy reagent.

Bottom Line: Dendritic cells (DCs) play a critical role in triggering anti-tumor immune responses.In this study, we identified microRNA-22 (miR-22) as a microRNA inhibiting p38 protein expression by directly binding to the 3' untranslated region (3'UTR) of its mRNA.The p38 down-regulation further interfered with the synthesis of DC-derived IL-6 and the differentiation of DC-driven Th17 cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Nankai University School of Medicine, Tianjin, China; Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China.

ABSTRACT
Dendritic cells (DCs) play a critical role in triggering anti-tumor immune responses. Their intracellular p38 signaling is of great importance in controlling DC activity. In this study, we identified microRNA-22 (miR-22) as a microRNA inhibiting p38 protein expression by directly binding to the 3' untranslated region (3'UTR) of its mRNA. The p38 down-regulation further interfered with the synthesis of DC-derived IL-6 and the differentiation of DC-driven Th17 cells. Moreover, overexpression of miR-22 in DCs impaired their tumor-suppressing ability while miR-22 inhibitor could reverse this phenomenon and improve the curative effect of DC-based immunotherapy. Thus, our results highlight a suppressive role for miR-22 in the process of DC-invoked anti-tumor immunity and that blocking this microRNA provides a new strategy for generating potent DC vaccines for patients with cancer.

No MeSH data available.


Related in: MedlinePlus