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Sci Rep. 2017 Jun 26;7(1):4247. doi: 10.1038/s41598-017-04434-w.

Gga-miR-219b targeting BCL11B suppresses proliferation, migration and invasion of Marek's disease tumor cell MSB1.

Author information

1
Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
2
College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin, 300384, China.
3
Division of Avian Infectious Diseases, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, 150001, China.
4
Department of Animal & Avian Sciences, University of Maryland, College Park, Maryland, 20742, United States.
5
Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China. lianlinglara@126.com.
6
Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China. nyang@cau.edu.cn.

Abstract

Marek's disease (MD), caused by Marek's disease virus (MDV), is a lymphotropic neoplastic disease. Previous miRNAome analysis showed gga-miR-219b was significantly downregulated in MDV-induced lymphoma, and one of its potential target genes, B-cell chronic lymphocytic /lymphoma 11B (BCL11B) was predicted. In this study, we further investigated the function of gga-miR-219b, and the gain/loss of function assay showed gga-miR-219b inhibited cell migration and reduced cell proliferation by promoting apoptosis not by cell cycle arrest. Gga-miR-219b also suppressed expression of two cell invasion-related genes MMP2 and MMP9. The results indicated suppressive effect of gga-miR-219b on MD tumorigenesis. The gene BCL11B was verified as a direct target gene of gga-miR-219b. RNA interference was performed to block BCL11B. As expected, the effects triggered by BCL11B downregulation were in accordance with that triggered by gga-miR-219b overexpression, suggesting that BCL11B was a stimulative regulator of MD transformation. Moreover, both gga-miR-219b and BCL11B influenced the expression of Meq gene, the most important oncogene in MDV. Additionally, gene expression level of anti-apoptotic genes BCL2 and BCL2L1 was downregulated and pro-apoptotic gene TNFSF10 was upregulated in MSB1 cells with gga-miR-219b overexpression or BCL11B knockdown, which suggested gga-miR-219b promoted cell apoptosis via regulating gene expression in the apoptosis pathways.

PMID:
28652615
PMCID:
PMC5484716
DOI:
10.1038/s41598-017-04434-w
[Indexed for MEDLINE]
Free PMC Article

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