Nasopharyngeal carcinoma progression is mediated by EBER-triggered inflammation via the RIG-I pathway.

Abstract

EBERs (EBER1 and EBER2) are suggested to be involved in cellular transformation and tumor growth. Cytoplasmic pattern recognition receptor-RIG-I, which is characterized by the recognition of viral dsRNAs, could efficiently trigger the downstream pathways of innate immunity. Although some previous reports have shown that EBERs and RIG-I associate with hematological malignancies, the role of EBERs-RIG-I signaling in solid tumors remains to be clarified. Here we demonstrate that EBER mediation of the inflammatory response via RIG-I contributes to NPC development in vitro and in vivo. We first verified that the expression level of RIG-I was associated with EBER transcription in a dose-dependent manner in NPC cells and specimens from NPC patients. Furthermore, pro-inflammatory cytokine transcription and release were sharply reduced after RIG-I knockdown compared with the control shRNA group in the presence of EBERs, accompanied by an attenuation of the NF-κB and MAPK signaling pathways. Consequently, the tumor burden was greatly alleviated in the RIG-I knockdown group in a xenograft model. In addition, macrophage colony-stimulating factor (M-CSF) and monocyte chemoattractant protein (MCP-1), which promote the maturation and attraction of tumor-associated macrophages, were stimulated upon the introduction of EBERs, and this upregulation conceivably led to the tumor-promoting subset transition of the macrophages. Taken together, our results reveal that EBERs could promote NPC progression through RIG-I-mediated cancer-related inflammation.

• Authors: Yumei Duan, Zhi Li, Shiyue Cheng, Yan Chen, Lu Zhang, Jiang He, Qiong Liao, Lifang Yang, Zhicheng Gong, Lun-Quan Sun
• Journal: Cancer letters (Cancer Lett) Vol. 361 Issue 1 Pg. 67-74 (May 28 2015) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 25721089 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Cytokines
• Epstein-Barr virus encoded RNA 1
• Epstein-Barr virus encoded RNA 2
• IRF3 protein, human
• Inflammation Mediators
• Interferon Regulatory Factor-3
• NF-kappa B
• RNA, Messenger
• RNA, Small Interfering
• RNA, Viral
• Receptors, Immunologic
• DDX58 protein, human
• DEAD Box Protein 58
• DEAD-box RNA Helicases

Topics

• Animals
• Blotting, Western
• Carcinoma
• Cell Differentiation
• Coculture Techniques
• Cytokines (genetics, metabolism)
• DEAD Box Protein 58
• DEAD-box RNA Helicases (antagonists & inhibitors, genetics, metabolism)
• Disease Progression
• Female
• Humans
• Immunoenzyme Techniques
• Immunoprecipitation
• Inflammation (immunology, metabolism, pathology)
• Inflammation Mediators (analysis)
• Interferon Regulatory Factor-3 (genetics, metabolism)
• Macrophages (immunology, metabolism, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• NF-kappa B (genetics, metabolism)
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms (immunology, metabolism, pathology)
• RNA, Messenger (genetics)
• RNA, Small Interfering (genetics)
• RNA, Viral (antagonists & inhibitors, genetics, metabolism)
• Real-Time Polymerase Chain Reaction
• Receptors, Immunologic
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Cells, Cultured
• Tumor Microenvironment
• Xenograft Model Antitumor Assays