High intensity focused ultrasound enhances anti-tumor immunity by inhibiting the negative regulatory effect of miR-134 on CD86 in a murine melanoma model
| Autor: | Jinyong Luo, Min Yang, Yue Gu, Liang Duan, Chongyan Li, He Zha, Yan Wang, Huan Li, Aifang Li, Tong-Chuan He, Zhibiao Wang, Shimei Yuan, Xueru Li, Lan Zhou, Hui Sun |
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| Rok vydání: | 2015 |
| Předmět: |
Lung Neoplasms
Ultrasonic Therapy Blotting Western Melanoma Experimental Apoptosis anti-tumor immunity Real-Time Polymerase Chain Reaction Mice Immune system Immunity Tumor Cells Cultured medicine Animals Humans RNA Messenger Cell Proliferation Ultrasonography CD86 Gene knockdown microRNA Reverse Transcriptase Polymerase Chain Reaction business.industry Cell growth Melanoma HIFU Transfection co-stimulatory molecules Flow Cytometry medicine.disease Xenograft Model Antitumor Assays Mice Inbred C57BL MicroRNAs Oncology Immunology Cancer research Female B7-2 Antigen business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.5285 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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