High intensity focused ultrasound enhances anti-tumor immunity by inhibiting the negative regulatory effect of miR-134 on CD86 in a murine melanoma model

HIFU has been demonstrated to enhance anti-tumor immunity, however, the mechanism of which has not been well elucidated. Emerging evidence indicates that miRNAs play important roles in immune response. In this study, we used the B16F10 melanoma allograft mouse model to investigate the role of miRNAs...

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Bibliographic Details
Published in:Oncotarget 2015-11, Vol.6 (35), p.37626-37637
Main Authors: Yuan, Shi-Mei, Li, Huan, Yang, Min, Zha, He, Sun, Hui, Li, Xue-Ru, Li, Ai-Fang, Gu, Yue, Duan, Liang, Luo, Jin-Yong, Li, Chong-Yan, Wang, Yan, Wang, Zhi-Biao, He, Tong-Chuan, Zhou, Lan
Format: Article
Language:English
Subjects:
Animals
Apoptosis - genetics
Apoptosis - radiation effects
B7-2 Antigen - antagonists & inhibitors
B7-2 Antigen - genetics
B7-2 Antigen - metabolism
Blotting, Western
Cell Proliferation - genetics
Cell Proliferation - radiation effects
Female
Flow Cytometry
Humans
Lung Neoplasms - diagnostic imaging
Lung Neoplasms - genetics
Lung Neoplasms - immunology
Lung Neoplasms - secondary
Melanoma, Experimental - diagnostic imaging
Melanoma, Experimental - genetics
Melanoma, Experimental - immunology
Melanoma, Experimental - pathology
Mice
Mice, Inbred C57BL
MicroRNAs - genetics
Real-Time Polymerase Chain Reaction
Research Paper
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
Tumor Cells, Cultured
Ultrasonic Therapy
Ultrasonography
Xenograft Model Antitumor Assays
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Summary:HIFU has been demonstrated to enhance anti-tumor immunity, however, the mechanism of which has not been well elucidated. Emerging evidence indicates that miRNAs play important roles in immune response. In this study, we used the B16F10 melanoma allograft mouse model to investigate the role of miRNAs in HIFU-enhanced anti-tumor immunity. We found that HIFU treatment decreased circulating B16F10 cells and pulmonary metastasis nodules while increased IFN-γ and TNF-α in the peripheral blood and cumulative mouse survival, which was associated with inhibition of miR-134 expression and activation of CD86 expression in tumor tissues. Further, we determined that miR-134 directly binds to the 3'UTR of CD86 mRNA to suppress its expression in B16F10 cells. When B16F10 cells transfected with miR-134 were co-cultured with normal splenic lymphocytes, the secretion of IFN-γ and TNF-α from lymphocytes was reduced and B16F10 cell survival was increased. HIFU exposure efficiently decreased miR-134 while increased CD86 expression in B16F10 cells in vitro. CD86 knockdown with siRNA markedly rescued the viability of HIFU-treated B16F10 cells that co-cultured with lymphocytes. Altogether, our results suggest that HIFU down-regulates miR-134 to release the inhibition of miR-134 on CD86 in melanoma cells, thereby enhancing anti-tumor immune response.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.5285