PARG regulates the proliferation and differentiation of DCs and T cells via PARP/NF-κB in tumour metastases of colon carcinoma

The present study investigated the effect of poly(ADP-ribose) glycohydrolase (PARG) on the immune response in tumour metastases of colon carcinoma. CT26 cells were transfected with lentivirus PARG-short hairpin RNA (shRNA). A liver metastasis model of colon carcinoma was successfully established by splenic subcapsular inoculation of the various groups of CT26 cells into BALB/c mice. Next, changes in the liver metastases of colon carcinoma nodules and alterations in the survival times were observed in tumour-bearing mice. The numbers of B220(+)DEC205(+) dendritic cells (B220(+)DEC205(+)DC) and CD11c(+)CD11b(+) dendritic cells (CD11c(+)CD11b(+)DC) in the spleen and liver were measured by the double-label immunofluorescence assay. The distribution pattern of CD4(+)T cells and CD8(+)T cells in the spleen and liver was investigated by immunofluorescence staining. The expression levels of PARG, PARP and nuclear factor-κB (NF-κB) proteins in spleen transplant tumours and liver metastases of colon carcinoma were detected by western blotting. An ELISA was used to detect the levels of IL-10 and TGF-β in the serum of tumour-bearing mice and from the supernatant of tumour cells. The numbers and grading of metastatic liver nodules in the PARG-silenced group were clearly lower than those in the control group. The survival time of the PARG-silenced group mice was longer than that in the control group. In the PARG-silenced group, the levels of B220(+)DEC205(+)DC in the spleen and liver were lower and the numbers of CD11c(+)CD11b(+)DC in the spleen and liver were more than those in the control group. The ratio of CD4(+)/CD8(+) in the spleen and liver in the PARG-silenced group was increased compared with that in the control group (P<0.05). The levels of PARG, PARP and NF-κB in spleen transplant tumours and liver metastases of colon carcinoma were lower in the PARG-silenced group than in the control group. In addition, the levels of IL-10 and TGF-β in the serum of tumour-bearing mice and supernatants of tumour cells were both reduced in the PARG-silenced group compared with those in the control group. The present research suggests that the liver metastases of colon carcinoma could be restrained by silencing PARG. Likely, the silencing of PARG could suppress the expression of PARP and NF-κB and subsequently suppress the secretion of IL-10 and TGF-α, finally affecting the proliferation and differentiation of DC and T cells.