lncRNA-803 Suppresses Apoptosis in DF-1 Cells via the miR-6555-3p/MDM4/p53 Axis

Long non-coding RNAs (lncRNAs) are integral to the regulation of viral tumorigenesis. We have previously identified that the chicken lncRNA-803, which responds to Marek's disease virus (MDV), inhibits apoptosis in the chicken embryonic fibroblast cell line DF-1, accompanied by changes in the expression of the p53 protein. Nonetheless, the molecular mechanism of lncRNA-803 in apoptosis has yet to be elucidated.

In this study, through lentivirus-mediated overexpression and knockdown experiments, we determined that the overexpression of lncRNA-803 induces elevated expression levels of murine double minute 2 (MDM2), murine double minute 4 (MDM4), tumor protein p53 (p53), and tumor protein p53 binding protein 1 (TP53BP1) within the p53 signaling pathway.

This modulation subsequently leads to an upregulation of B-cell lymphoma-2 (Bcl-2) expression, while concurrently resulting in the downregulation of cysteinyl aspartate specific proteinase 8 (Caspase-8), cysteinyl aspartate specific proteinase 9 (Caspase-9), Bcl-2 associated protein X (Bax), and cysteinyl aspartate specific proteinase 9 (Caspase-3) in the apoptosis pathway. In terms of its mechanism, lncRNA-803 functions as a molecular sponge for miR-6555-3p. lncRNA-803 engages in competitive binding with miR-6555-3p, thereby diminishing its inhibitory effect on MDM4.

These results elucidate that lncRNA-803 modulates apoptosis in DF-1 cells through a novel competing endogenous RNA mechanism involving the miR-6555-3p/MDM4/p53 axis. These findings provide new insights into the molecular pathogenesis of MDV.