DIRAS2 promotes radiation resistance in renal cell carcinoma via autophagy induction and MKK4-JNK1 pathway activation

Background: to investigate the effect of diras2 on the response to ionizing radiation (ir) and the related potential molecular mechanism in human ccrcc cells. materials and methods: in this paper, the expression levels of diras2 in human ccrcc and paired normal tissues were obtained from the oncomine platform and the cancer genome atlas (tcga) database, which was further validated by immunohistochemistry. diras2-overexpression cell lines were constructed using a lentivirus-mediated gene expression system. a clonogenic assay was performed to evaluate cell radiation resistance. the effect of diras2 on autophagy was determined by immunoblotting and immunofluorescence analysis. the expression of diras2 and related signalling molecules was evaluated by immunoblotting. results: here, we found that the expression of diras2 was upregulated in human ccrcc. overexpression of diras2 promoted radiation resistance in ccrcc cells and enhanced the levels of radiation-induced autophagy. moreover, inhibition of autophagy by chloroquine (cq) pretreatment largely eliminated the effect of diras2 overexpression on radiation resistance. finally, molecular mechanism investigation showed that diras2 activated the mitogen-activated protein kinase (mapk) kinase 4 (mkk4)-c-jun nh2-terminal kinase 1 (jnk1)-bcl-2 pathway. conclusion: taken together, these results indicated that diras2 may confer radiation resistance to human rcc via autophagy induction through the mkk4-jnk1-bcl-2 signalling pathway.