The inhibitory effects of gga-miR-199-3p, gga-miR-140-3p, and gga-miR-221-5p in Marek's disease tumorigenesis.

Marek's disease (MD) is lymphoproliferative neoplastic disease in chickens, which is caused by Marek's disease virus (MDV). Our previous study profiled microRNA (miRNA) transcriptome in MD lymphoma, and found that gga-miR-199-3p, gga-miR-140-3p, and gga-miR-221-5p were down-regulated in MD lymphoma. In this study, we further investigated their differential expression between MDV-infected spleens and noninfected spleens at 4, 7, 14, 21, and 28 d postinfection (dpi) to elucidate whether deregulation of them was specific to late tumor transformation phase or not. The results showed that gga-miR-199-3p was down-regulated at 14 and 28 dpi, and the expression of gga-miR-140-3p was decreased at 14 dpi, which indicated that deregulation of these miRNAs appeared since early stage of MD tumor transformation. Additionally, the inhibitory effects of gga-miR-199-3p, gga-miR-140-3p, and gga-miR-221-5p on MDV-transformed lymphoid cell line (MSB1) cells proliferation were observed, which suggested that these miRNAs acted as MD tumor suppressors. Their aberrant expression at early tumor transformation phase and suppressive role in cell proliferation indicated that they were involved in MD lymphoma transformation, and might play crucial roles in MD tumorigenesis.