Abstract
This study aimed to explore the mutual regulation between chicken telomerase reverse transcriptase (chTERT) and the Wnt/β-catenin signalling pathway and its effects on cell growth and avian leukosis virus subgroup J (ALV-J) replication in LMH cells. First, LMH cells stably overexpressing the chTERT gene (LMH-chTERT cells) and corresponding control cells (LMH-NC cells) were successfully constructed with a lentiviral vector expression system. The results showed that chTERT upregulated the expression of β-catenin, Cyclin D1, TCF4 and c-Myc. chTERT expression level and telomerase activity were increased when cells were treated with LiCl. When the cells were treated with ICG001 or IWP-2, the activity of the Wnt/β-catenin signalling pathway was significantly inhibited, and chTERT expression and telomerase activity were also inhibited. However, when the β-catenin gene was knocked down by small interfering RNA (siRNA), the changes in chTERT expression and telomerase activity were consistent with those in cells treated with ICG001 or IWP-2. These results indicated that chTERT and the Wnt/β-catenin signalling pathway can be mutually regulated. Subsequently, we found that chTERT not only shortened the cell cycle to promote proliferation but also inhibited apoptosis by downregulating the expression of Caspase 3, Caspase 9 and BAX; upregulating BCL-2 and BCL-X expression; and promoting autophagy. Moreover, chTERT significantly enhanced the migration ability of LMH cells, upregulated the protein and mRNA expression of ALV-J and increased the virus titre. ALV-J replication promoted chTERT expression and telomerase activity.
Highlights
Telomerase is a ribonucleoprotein enzyme that adds tandem (TTAGGG)n repeats to the ends of chromosomes in most eukaryotes [1]
The results showed that the mRNA and protein expression levels of chicken telomerase reverse transcriptase (chTERT) were significantly higher in LMH-chTERT cells than in control cells (Figure 1A; p < 0.0001)
The results showed that chTERT expression was significantly higher in cells infected with avian leukosis viruses (ALVs)-J at an multiplicity of infection (MOI) of 0.1 or 1.0 than in control cells (Figure 9E and F; p < 0.05) and that telomerase activity was increased in infected cells, indicating that ALV subgroup J (ALV-J) can promote the expression of chTERT
Summary
Telomerase is a ribonucleoprotein enzyme that adds tandem (TTAGGG)n repeats to the ends of chromosomes in most eukaryotes [1]. Subgroup A and B viruses mainly cause lymphocytic leukaemia and myeloid leukosis in field flocks, while flocks naturally infected with subgroup C and D viruses are rarely observed in the field. The chTERT gene was identified as a common insertion site in myeloid leukosis caused by ALV-J, and the gene expression of chTERT, a putative driver for oncogene activation, was significantly upregulated in tumour samples compared to control samples [24]. It is not clear whether chTERT affects ALV-J replication and what effect ALV-J has on chTERT
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