Biological function and potential mechanism of dicarbonyl and L-xylulose reductase in the occurrence and development of renal cell carcinoma
Objective:To investigate the role and potential mechanism of glucuronate metabolism-related en-zyme dicarbonyl and L-xylulose reductase(DCXR)in the proliferation and migration of human clear cell renal cell carcinoma(ccRCC)cells,and to detect the clinical relevance of DCXR expression level in patients with renal cell carcinoma.Methods:Bioinformatics was used to detect the expression of DCXR in pan-cancer and renal cell carci-noma.Quantitative real-time PCR(qRT-PCR)and Western blotting were used to detect the expression of DCXR in ccRCC tissues of 30 cases and paired adjacent tissues collected from First Medical Center of PLA General Hos-pital from June 30th,2022 to January 30th,2023,as well as in human ccRCC cell lines 786-O,ACHN and human embryonic kidney cell line 293T.The overexpression vector of DCXR was transfected into 786-O and ACHN cells,and the overexpression efficiency was detected by qRT-PCR and Western blotting.Cell Counting Kit-8(CCK-8)experiment and colony formation experiment were used to detect cell proliferation.Wound healing exper-iment and Transwell experiment were used to detect cell migration.Immunohistochemical staining and clinical rel-evance analysis were performed on renal cell carcinoma tissue chips.Finally,GSEA enrichment analysis was used to predict the signaling pathway in which DCXR may be involved.Results:Bioinformatics showed that DCXR was significantly down-regulated in renal cell carcinoma.In mRNA and protein levels,the expression of DCXR in tumor tissues was lower than that in paired adjacent renal tissues,and the difference was statistically significant(P<0.05).The expressions of DCXR in renal cancer cells 786-O and ACHN were lower than those in human em-bryonic kidney cells.The proliferation activity and cell clone rate of 786-O and ACHN cells in the overexpression DCXR group were lower than those in the control empty vector control group,with statistically significant differ-ences(P<0.05).The scratch healing area and Transwell cell migration number of 786-O and ACHN cells in the overexpression DCXR group were lower than those in the empty vector control group,with statistically significant differences(P<0.05).Through the analysis of tissue microarray staining and related clinical data of ccRCC in our center,the expression of DCXR was correlated with the prognosis of ccRCC(P<0.05).Conclusion:The expres-sion of DCXR is decreased in ccRCC,and overexpression of DCXR can inhibit the cell proliferation and migration ability of ccRCC,which may be used as a biological marker to predict the prognosis of patients.
dicarbonyl and L-xylulose reductaseclear cell renal cell carcinomaproliferationmigration