Expression and clinical significance of DCN1-like protein 3 mediated neddylation pathway in bladder urothelial carcinoma
Objective To detect the expression level of neural precursor cell expressed develop-mentally downregulated 8(NEDD8),DCN1-like protein 3(DCNL3)and ubiquitin conjugating enzyme E2M(UBE2M)in the different clinical stages of bladder urothelial carcinoma,observe the effect of DCNL3 on the neddylation of Cullin1 and Cullin3 skeleton protein by interfering with DCNL3 expression,and ex-plore the relationship between neddylation pathway mediated by DCNL3 and clinical pathological features of bladder urothelial carcinoma.Methods In total,59 bladder urothelial carcinoma specimens that were sur-gically resected and pathologically confirmed from the First Affiliated Hospital of Zhengzhou University from March 2020 to May 2023 were selected.Cancer tissue center and its distal normal mucosa were used as controls for each specimen.Real-time fluorescence quantitative reverse transcription-polymerase chain reac-tion(RT-PCR)and immunohistochemical techniques were used to detect the expression of NEDD8,DCNL3 and UBE2M in excised specimens.The levels of Cullin1 and Cullin3 in bladder cancer cell line T24 were detected by overexpression/silencing of DCNL3 gene and Western blotting.The clinicopathologic features of the patients were analyzed by x2 test.Results The expression rate of NEDD8,DCNL3 and UBE2M was significantly higher in bladder urothelial carcinoma than in normal tissues(0.613±0.167 vs.0.985±0.205,1.223±0.558 vs.1.874±0.245,1.639±0.212 vs.2.187±0.335,t=1.933,2.142,2.025,P＜0.05).The expression rate of NEDD8,DCNL3 and UBE2M in muscle invasive blad-der cancer group was significantly higher than that in non-muscle invasive group(0.738±0.188 vs.1.245±0.155,1.566±0.385 vs.2.532±0.466,1.933±0.485 vs.2.748±0.515,t=2.106,2.767,2.367,P＜0.05),which was related with the degree of tumor differentiation and tumor depth of invasion.High expression of DCNL3 promoted substrate protein Cullin1[(78.55±6.34)％vs.(35.15±5.32)％,t=26.22,P＜0.05],and Cullin3[(66.82±5.66)％vs.(22.52±4.66)％,t=22.05,P＜0.05]neddylation.Conclusion The expression of DCNL3 was related with the clinical stages of bladder urothelial carcinoma through the regulation of Cullin1/Cullin3 neddylation,which mediates the development of bladder urothelial carcinoma.
DCN1-like protein 3Cullin1Cullin3NeddylationBladder urothelial carci-noma
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