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

Abstract

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.