POLD1在膀胱癌细胞增殖和迁移中的作用机制及其临床应用潜力OA北大核心

Objective:To investigate the expression of DNA polymerase δ catalytic subunit gene 1(POLD1)in bladder cancer tissues and its correlation with patients'clinicopathological characteristics and prognosis,and to explore its effect on the proliferation,migration,and invasion of bladder cancer 5637 cells.Methods:Sixty cases of bladder cancer tissues and paired adjacent noncancerous tissues preserved in the Department of Pathology,Shanxi Bethune Hospital,from January to June 2021 were collected.Immunohistochemistry was performed to detect POLD1 protein expression in bladder cancer tissues.Patients were divided into high-and low-expression groups according to POLD1 levels,and the correlations between POLD1 level with clinicopathological characteristics and prognosis were analyzed.Bladder cancer 5637 cells were cultured routinely and divided into a control group(untransfected),a sh-NC group(transfected with sh-NC-GFP lentivirus vector),and a sh-POLD1 group(transfected with sh-POLD1-GFP lentiviral vector).Transfection efficiency was validated using fluorescence microscopy and WB method.Cell proliferation,migration,and invasion were assessed using CCK-8,wound-healing,and Transwell assays.5637 cell-transplanted tumor experiment was performed to detect the effect of POLD1 knockdown on the growth of transplanted tumors.Results:POLD1 was highly expressed in bladder cancer tissues(P<0.05).High POLD1 expression was significantly associated with advanced clinical stage and pathological grade(all P<0.05).Patients with high POLD1 expression exhibited shorter progression-free survival,reduced overall survival,lower 3-year survival rate,and higher recurrence and metastasis rate(all P<0.05).The expression of POLD1 was successfully knocked down in 5637 cells,which significantly inhibited the proliferation,migration,and invasion abilities of 5637 cells(all P<0.05).In vivo,POLD1 knockdown significantly inhibited the growth of transplanted tumors(P<0.05).Conclusion:POLD1 is highly expressed in bladder cancer tissues,and its upregulation is associated with tumor stage,pathological grade,and patient prognosis.POLD1 knockdown can inhibit the malignant biological behaviors of bladder cancer cells.