Molecular Mechanism of FAdV-4 Inducing Apoptosis of Chicken Hepatocytes through lnc87774-MDM2-p53 Pathway

Xiao Yaqing; Dong Wenwen; Yuan Xiaoyuan; Li Guiming; Liu Mingchao; Meng Kai

doi:10.14083/j.issn.1001-4942.2025.01.020

Abstract：Pericardial effusion hepatitis syndrome caused by fowl adenovirus serotype 4(FAdV-4)has occurred frequently in China in recent years,causing huge losses to China's poultry industry.The lncRNA is a key regulator of host immune response during viral infection.In order to reveal its effect and mechanism on host cells during FAdV-4 infection,the chicken liver cancer cell line LMH was used as object in this study.The key lncRNA molecules during viral infection were screened by chip sequencing,bioinformatics analysis and Real-time PCR.Subcellular localization analysis and interaction protein screening,verification and func-tional analysis were performed by fluorescence localization hybridization,coding-non-coding gene co-expres-sion analysis(CNC),real-time PCR,enzyme-linked immunosorbent assay(ELISA),RNA pull-down and protein immunoprecipitation(RIP),flow cytometry and other molecular biological methods.The results showed that the key lncRNA molecule lnc87774 caused by FAdV-4 infection was screened out,which was mainly located in cytoplasm,and its target binding interaction protein was E3 ubiquitin ligase MDM2.Overex-pression of lnc87774,the relative expression of MDM2 and Bcl-2 increased significantly,and that of p53 and Bax decreased significantly,which significantly inhibited cell apoptosis.Silencing lnc87774,the above genes showed the opposite change trend and significantly promoted cell apoptosis.After further silencing MDM2,the expression of p53 was significantly up-regulated,but overexpression/silencing of lnc87774 had no effect on FAdV-4-induced cell apoptosis,indicating that lnc87774 targeted p53-mediated cell apoptosis through MDM2 during FAdV-4 infection of LMH cells.The results of this study could increase our understanding of the inter-action between FAdV-4 and host cells and provide theoretical support for the host antiviral defense mechanism.