Effect of gga-miR-155 on cell proliferation, apoptosis and invasion of Marek\u2019s disease virus (MDV) transformed cell line MSB1 by targeting RORA

Ke Ding,Cheng-Shui Liao,Zu-Ling Yu,Yan-Yan Jia,Zi-Yu Zhou,Xiang-Chao Cheng,Chuan Yu,Ting-Cai Wu,Lei He,Jing Li,Chun-Jie Zhang,Zu-Hua Yu,Yin-Ju Li

doi:10.1186/s12917-020-2239-4

Ke Ding, Cheng-Shui Liao + Show 11 more

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https://doi.org/10.1186/s12917-020-2239-4

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Abstract

BackgroundMarek’s disease (MD) is caused by the oncogenic Marek’s disease virus (MDV), and is a highly contagious avian infection with a complex underlying pathology that involves lymphoproliferative neoplasm formation. MicroRNAs (miRNAs) act as oncogenes or tumor suppressors in most cancers. The gga-miR-155 is downregulated in the MDV-infected chicken tissues or lymphocyte lines, although its exact role in tumorigenesis remains unclear. The aim of this study was to analyze the effects of gga-miR-155 on the proliferation, apoptosis and invasiveness of an MDV-transformed lymphocyte line MSB1 and elucidate the underlying mechanisms.ResultsThe expression level of gga-miR-155 was manipulated in MSB1 cells using specific mimics and inhibitors. While overexpression of gga-miR-155 increased proliferation, decreased the proportion of G1 phase cells relative to that in S and G2 phases, reduced apoptosis rates and increased invasiveness. However, its downregulation had the opposite effects. Furthermore, gga-miR-155 directly targeted the RORA gene and downregulated its expression in the MSB1 cells.ConclusionThe gga-miR-155 promotes the proliferation and invasiveness of the MDV-transformed lymphocyte line MSB1 and inhibits apoptosis by targeting the RORA gene.

Highlights

Marek’s disease (MD) is caused by the oncogenic Marek’s disease virus (MDV), and is a highly contagious avian infection with a complex underlying pathology that involves lymphoproliferative neoplasm formation
Gga-miR-155 promotes the proliferation and cell cycle progression of MSB1 cells To determine the role of gga-miR-155 in MDVtransformed T cells, we respectively overexpressed and downregulated the miRNA in MSB1 cells using mimics and inhibitors (Fig. 1)
Gga-miR-155 inhibits apoptosis of MSB1 cells To determine the effect of gga-miR-155 on apoptosis, the percentage of apoptotic MSB1 cells was evaluated 48 h after transfecting with the different constructs

Summary

Introduction

Marek’s disease (MD) is caused by the oncogenic Marek’s disease virus (MDV), and is a highly contagious avian infection with a complex underlying pathology that involves lymphoproliferative neoplasm formation. Marek’s disease virus (MDV) is an oncogenic herpesvirus, reclassified as the Gallid alphaherpesvirus 2 (GaHV2) [1] It is the causative agent of Marek’s disease (MD), which is characterized by complex clinical syndromes, including immune suppression, paralysis, neurological signs and lesions, and the rapid formation of CD4+ T-cell lymphomas [2,3,4], and is responsible for considerable losses to the poultry industry worldwide. A vaccine is available against MD, eruptions are common even in immunized chicken flocks, likely due to intensive farming, incomplete immunization and increasing virulence [5,6,7,8] It MicroRNAs (miRNAs) are endogenous small noncoding RNA that degrade mRNAs or inhibit translation by binding to their 3′-untranslated regions (3′-UTR), and regulate multiple cellular processes, such as proliferation, cell cycle, apoptosis, migration and metabolism [9,10,11,12,13]. MiRNA-155 is a conserved multifunctional cellular miRNA that regulates the proliferation, migration and invasive growth of tumor cells, and is closely associated with tumor initiation and progression [18,19,20,21], Studies show that the MD-encoded miR-M4-5p is the viral ortholog of cellular miR-155, and shares common targets with miR-155 and

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