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Chicken lncRNA-9802 Induces the S Phase Arrest in the T Lymphocyte Cells Infected by Marek's Disease Virus via the
Shuo Han1,2, Haile Ren2, Jingyi Yang2
1Engineering Laboratory for Tarim Animal Diseases Diagnosis and Control, College of Animal Science and Technology, Tarim University, Alar 843300, China.
Abstract:
The oncogenic Marek's disease virus (MDV) triggers Marek's disease (MD), which is a substantial threat to poultry as it transforms infected T cells into tumors. Our research identified that long non-coding RNA 9802 (lncRNA-9802) exhibits increased expression in the chicken spleen following MDV infection, with its expression being strongly associated with the expression of tumor p53-binding protein 1 (TP53BP1). The function of lncRNA-9802 in T cells transformed by MDV remains unclear. Consequently, the expression levels of lncRNA-9802 were either over-expressed or knocked down in MDV-transformed T cells, MDCC-MSB1, through lentivirus-mediated over-expression and knock down experiments. Our findings demonstrate that lncRNA-9802 induces proliferation disturbances in MDCC-MSB1 cells by causing arrest in the S phase, which is accompanied by increased expression levels of TP53BP1, p53, and p21. Activation of the p53 pathway results in elevated levels of Cyclin E and Cyclin-dependent kinase 2 (CDK2), thereby facilitating the entry of MDCC-MSB1 cells into the S phase. Concurrently, the reduced levels of Cyclin A inhibit the exit of MDCC-MSB1 cells from the S phase. By modulating the TP53BP1/p53/p21 pathway, lncRNA-9802 induces S phase arrest in MDCC-MSB1 cells, characterized by upregulation of Cyclin E and CDK2 and downregulation of Cyclin A. This research enhances the understanding of the pathogenic mechanisms of MDV and provides a foundation for identifying potential targets for antiviral drug development.
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