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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 is expressed and functions in dendritic cells (DCs).(A) miR-22 expression level was examined using real-time RT-PCR and this microRNA was found to be distributed in a wide range of cells, including mouse splenocytes, bone marrow cells (BMCs), BMC derived DCs and murine monocyte/macrophage cell line RAW264.7. The great increase of miR-22 level after BMCs being induced to DCs was reminiscent of a close relationship between this mircoRNA and the process of DC differentiation. (B, C, D) Similar to the RAW264.7 model, miR-22 exhibited an inhibitory effect on p38 protein expression in DCs. After 48 h of miR-22 mimics or inhibitor transfection, p38 levels were probed by WB. The gray scale of p38 band was negatively correlated with the dose of miR-22 mimics while positively correlated with the dose of miR-22 inhibitor. All the experiments in this figure were performed at least 3 times. The real-time RT-PCR result in (A) is expressed as mean±SD.
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pone.0121510.g003: miR-22 is expressed and functions in dendritic cells (DCs).(A) miR-22 expression level was examined using real-time RT-PCR and this microRNA was found to be distributed in a wide range of cells, including mouse splenocytes, bone marrow cells (BMCs), BMC derived DCs and murine monocyte/macrophage cell line RAW264.7. The great increase of miR-22 level after BMCs being induced to DCs was reminiscent of a close relationship between this mircoRNA and the process of DC differentiation. (B, C, D) Similar to the RAW264.7 model, miR-22 exhibited an inhibitory effect on p38 protein expression in DCs. After 48 h of miR-22 mimics or inhibitor transfection, p38 levels were probed by WB. The gray scale of p38 band was negatively correlated with the dose of miR-22 mimics while positively correlated with the dose of miR-22 inhibitor. All the experiments in this figure were performed at least 3 times. The real-time RT-PCR result in (A) is expressed as mean±SD.

Mentions: Consistent with our previous report [19], the expression of miR-22 was not limited to RAW264.7 cell line, as shown by our real-time RT-PCR result. Mouse splenocytes, bone marrow cells (BMCs) and BMDCs also had an internal level of it. Notably, although the miR-22 content was low in murine BMCs, once they were induced in vitro into BMDCs, the amount of miR-22 would increase significantly. It was not clear whether it was the cause or the result of DC differentiation, but it was affirmative that miR-22 had a close relationship with the process of DC development (Fig 3A). Thus, to better illustrate the general function of miR-22 in dendritic cells, we next transfected the mimics or inhibitor of miR-22 into DCs and detected the protein level of p38. Similar to the case of RAW264.7 model, miR-22 exhibited an inhibitory effect on this target gene, the expression level of p38 decreased in the presence of the mimics while increased in the presence of the inhibitor (Fig 3B). The correlation or anti-correlation between p38 protein level and the dose of miR-22 inhibitor or mimics as revealed by the dose response further confirmed this effect (Fig 3C and 3D).


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 is expressed and functions in dendritic cells (DCs).(A) miR-22 expression level was examined using real-time RT-PCR and this microRNA was found to be distributed in a wide range of cells, including mouse splenocytes, bone marrow cells (BMCs), BMC derived DCs and murine monocyte/macrophage cell line RAW264.7. The great increase of miR-22 level after BMCs being induced to DCs was reminiscent of a close relationship between this mircoRNA and the process of DC differentiation. (B, C, D) Similar to the RAW264.7 model, miR-22 exhibited an inhibitory effect on p38 protein expression in DCs. After 48 h of miR-22 mimics or inhibitor transfection, p38 levels were probed by WB. The gray scale of p38 band was negatively correlated with the dose of miR-22 mimics while positively correlated with the dose of miR-22 inhibitor. All the experiments in this figure were performed at least 3 times. The real-time RT-PCR result in (A) is 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.g003: miR-22 is expressed and functions in dendritic cells (DCs).(A) miR-22 expression level was examined using real-time RT-PCR and this microRNA was found to be distributed in a wide range of cells, including mouse splenocytes, bone marrow cells (BMCs), BMC derived DCs and murine monocyte/macrophage cell line RAW264.7. The great increase of miR-22 level after BMCs being induced to DCs was reminiscent of a close relationship between this mircoRNA and the process of DC differentiation. (B, C, D) Similar to the RAW264.7 model, miR-22 exhibited an inhibitory effect on p38 protein expression in DCs. After 48 h of miR-22 mimics or inhibitor transfection, p38 levels were probed by WB. The gray scale of p38 band was negatively correlated with the dose of miR-22 mimics while positively correlated with the dose of miR-22 inhibitor. All the experiments in this figure were performed at least 3 times. The real-time RT-PCR result in (A) is expressed as mean±SD.
Mentions: Consistent with our previous report [19], the expression of miR-22 was not limited to RAW264.7 cell line, as shown by our real-time RT-PCR result. Mouse splenocytes, bone marrow cells (BMCs) and BMDCs also had an internal level of it. Notably, although the miR-22 content was low in murine BMCs, once they were induced in vitro into BMDCs, the amount of miR-22 would increase significantly. It was not clear whether it was the cause or the result of DC differentiation, but it was affirmative that miR-22 had a close relationship with the process of DC development (Fig 3A). Thus, to better illustrate the general function of miR-22 in dendritic cells, we next transfected the mimics or inhibitor of miR-22 into DCs and detected the protein level of p38. Similar to the case of RAW264.7 model, miR-22 exhibited an inhibitory effect on this target gene, the expression level of p38 decreased in the presence of the mimics while increased in the presence of the inhibitor (Fig 3B). The correlation or anti-correlation between p38 protein level and the dose of miR-22 inhibitor or mimics as revealed by the dose response further confirmed this effect (Fig 3C and 3D).

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