J Cancer 2017; 8(2):305-313. doi:10.7150/jca.15753
The Epstein-Barr Virus-encoded miR-BART22 targets MAP3K5 to promote host cell proliferative and invasive abilities in nasopharyngeal carcinoma
1. Department of Pathology, Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510150, PR, China;
2. Department of Pathology, Basic school, Guangzhou Medical University, Guangzhou,510000, PR China;
3. Cancer Research Institute, Southern Medical University, Guangzhou, 510515, PR China;
4. Gastrointestinal Department, Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510150, PR, China;
5. Department of obstetrics and gynecology, First affiliated hospital, Gannan medical university, Gannan,341000, PR, China.
* These authors contributed equally to this work.
miR-BART22, a new discovered Epstein-Barr virus (EBV) miRNA, is abundant in Nasopharyngeal carcinoma (NPC). It has been reported that miR-BART22 promoted the tumor development by down-modulating EBV LMP2 expression to evade the host immune response. But its cell target genes have still been obscure. We have reported an inverse correlation between the BART-22 and MAP3K5 protein expression in NPC tissues and NPC cell lines. Meanwhile, MAP3K5 protein expression level was significantly decreased in primary NPC tissues compared with nasopharyngitis when MAP3K5 mRNA expression was consistent in two group tissues. According to our data and target prediction by miRnada, we assume MAP3K5 is an important target gene of NPC. MAP3K5, also named apoptosis signal-regulating kinase1 (ASK1), is an important early answer gene in P38MAPK pathway and an apoptosis-related gene. In present study, MAP3K5 was verified the target gene of miR-BART22 by luciferase assay. miRBART-22 decreased MAP3K5 protein level. Moreover, it also decreased MAP3K5 downstream gene MAP2K4 expression in P38MAPK pathway, and even their activated phosphorylation forms. Additionally, we found stable transfection of miR-BAT22 could improve tumor cells' proliferative and invasive abilities in NPC cell line 5-8F. The data highlight the role of the EBV miR-BART22 in regulating genes involving in apoptosis and some important pathways to promote cancer development. And it also raises the possibility that inhibitors of miR-BART22 can be as a therapeutic strategy for NPC and other EBV-infected tumors treatment.
Keywords: Nasopharyngeal carcinoma, Epstein-Barr Virus, miRNA, MAP3K5.
Chen R, Zhang M, Li Q, Xiong H, Liu S, Fang W, Zhang Q, Liu Z, Xu X, Jiang Q. The Epstein-Barr Virus-encoded miR-BART22 targets MAP3K5 to promote host cell proliferative and invasive abilities in nasopharyngeal carcinoma. J Cancer 2017; 8(2):305-313. doi:10.7150/jca.15753. Available from http://www.jcancer.org/v08p0305.htm