Xu, Yuan-JiYuan-JiXuZhou, RuiRuiZhouZong, Jing-FengJing-FengZongLin, Wan-SongWan-SongLinTong, ShuangShuangTongGuo, Qiao-JuanQiao-JuanGuoCHENG-FANG LINLin, Shao-JunShao-JunLinChen, Yi-XinYi-XinChenMEI-RU CHENChen, Hong-LinHong-LinChenYe, Yun-BinYun-BinYePan, Jian-JiJian-JiPan2019-08-292019-08-292019-04-1003043835https://www.scopus.com/inward/record.uri?eid=2-s2.0-85060544670&doi=10.1016%2fj.canlet.2019.01.022&partnerID=40&md5=3f8775fd2cf5b10c24ed92d4e244fef7https://scholars.lib.ntu.edu.tw/handle/123456789/416795Based 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.enCell growth; Metastasis; NKIRAS2; Nasopharyngeal carcinoma; miR-BART13[SDGs]SDG3immunoglobulin enhancer binding protein; messenger RNA; microRNA; NKIRAS2 protein; regulator protein; unclassified drug; carrier protein; immunoglobulin enhancer binding protein; microRNA; virus RNA; animal cell; animal experiment; animal model; animal tissue; Article; BART13 gene; cancer growth; cancer tissue; carcinogenesis; cell invasion; cell proliferation; controlled study; epithelial mesenchymal transition; Epstein Barr virus; female; gene expression; gene targeting; human; human cell; human tissue; in vitro study; in vivo study; lung metastasis; metastasis; mouse; nasopharyngeal carcinoma cell line; nasopharynx carcinoma; NKIRAS2 gene; nonhuman; oncogene; phenotype; priority journal; protein expression; signal transduction; tumor growth; upregulation; animal; Bagg albino mouse; drug screening; Epstein Barr virus; Epstein Barr virus infection; gene expression regulation; genetics; HEK293 cell line; metastasis; nasopharynx carcinoma; nasopharynx tumor; nude mouse; procedures; signal transduction; tumor cell line; virology; Animals; Carrier Proteins; Cell Line, Tumor; Cell Proliferation; Epstein-Barr Virus Infections; Female; Gene Expression Regulation, Neoplastic; HEK293 Cells; Herpesvirus 4, Human; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Metastasis; NF-kappa B; RNA, Viral; Signal Transduction; Xenograft Model Antitumor Assaysjournal article10.1016/j.canlet.2019.01.022306845922-s2.0-85060544670WOS:000460711900004https://api.elsevier.com/content/abstract/scopus_id/85060544670