Epstein-Barr virus-coded miR-BART13 promotes nasopharyngeal carcinoma cell growth and metastasis via targeting of the NKIRAS2/NF-κB pathway.

Autor: Xu YJ; Department of Radiation Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China., Zhou R; Department of Radiation Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China., Zong JF; Department of Radiation Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China., Lin WS; Laboratory of Immune Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China; Fujian Provincial Key Laboratory of Translational Cancer Medicine, China., Tong S; State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China., Guo QJ; Department of Radiation Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China; Fujian Provincial Key Laboratory of Translational Cancer Medicine, China., Lin C; Department of Radiation Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China., Lin SJ; Department of Radiation Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China; Fujian Provincial Key Laboratory of Translational Cancer Medicine, China., Chen YX; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen, Fujian, China., Chen MR; Graduate Institute and Department of Microbiology, College of Medicine, National Taiwan University, Taiwan., Chen HL; State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China., Ye YB; Laboratory of Immune Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China; Fujian Provincial Key Laboratory of Translational Cancer Medicine, China. Electronic address: zjyunbin@189.cn., Pan JJ; Department of Radiation Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China; Fujian Provincial Key Laboratory of Translational Cancer Medicine, China. Electronic address: panjianji@aliyun.com.
Jazyk: angličtina
Zdroj: Cancer letters [Cancer Lett] 2019 Apr 10; Vol. 447, pp. 33-40. Date of Electronic Publication: 2019 Jan 23.
DOI: 10.1016/j.canlet.2019.01.022
Abstrakt: Based on analysis of Epstein-Barr virus (EBV) BART microRNA expression profiles, we previously reported that EBV-encoded miR-BART13 is upregulated in nasopharyngeal carcinoma (NPC) plasma specimens. However, the effects and molecular mechanisms of miR-BART13 in NPC remain largely unknown. We found that miR-BART13 was significantly upregulated in NPC tissue specimens. Ectopic expression of miR-BART13 promoted NPC cell proliferation, epithelial mesenchymal transition, and metastasis in vitro, and facilitated xenograft tumor growth and lung metastasis in vivo. Molecularly, NF-κB inhibitor interacting Ras-like 2 (NKIRAS2), a negative regulator of the NF-κB signaling, was identified to be a direct target of miR-BART13 in NPC cells, and NKIRAS2 mRNA and protein expression was inversely correlated with miR-BART13 in NPC tissues, respecitvely. Furthermore, the NF-κB signaling pathway was activated by miR-BART13. By rescued experiments, reconstitution of NKIRAS2 expression abrogated all the phenotypes upregulated by miR-BART13, and attenuated activity of NF-κB signaling pathway activated by miR-BART13 in NPC cells. Our findings indicated the newly identified miR-BART13/NKIRAS2/NF-κB signaling axis may provide further insights into better understanding of NPC initiation and development, and targeting of this pathway could be further studied as a therapeutic strategy for NPC patients.
(Copyright © 2019. Published by Elsevier B.V.)
Databáze: MEDLINE
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