Mechanism of PTTG binding factor regulation of MDM2/NIS expression in improving radioactive iodine uptake in thyroid cancer cells

XIA Huan; CHANG Cheng; WU Min; DONG Zhan-fei

doi:10.13820/j.cnki.gdyx.20242603

Abstract：Objective To investigate the effects of PTTG binding factor(PBF)regulation on murine double mi-nute 2(MDM2)and sodium/iodine symporter(NIS)expression and its impact on improving radioactive iodine uptake in thyroid cancer cells.Methods Lentiviral-mediated silencing of PBF protein expression was performed in TPC-1 thy-roid cancer cells,creating two groups:the PBF-shRNA group and the control group.Cell viability was assessed using the CCK-8 assay at days 1,3,5,and 7 after intervention.After exposure to Na131I(radioactive activity:0.185 Bq),radio-active iodine uptake was measured at the same time points.Western blot analysis was used to compare the relative expres-sion of MDM2 and NIS proteins between the two groups.Results Both groups exhibited a gradual increase in TPC-1 cell numbers over 1,3,5,and 7 days of culture(F=41.909,P＜0.001;F=108.711,P＜0.001).However,cell vi-ability in the PBF-shRNA group was significantly lower than in the control group on days 5 and 7[(59.4±7.1)％and(80.2±5.3)％,respectively,vs.(78.6±6.2)％and(98.5±4.8)％;t=-3.528,P=0.024;t=-4.433,P=0.011].On days 5 and 7,radioactive iodine uptake in the PBF-shRNA group was significantly higher[(1 022.3±80.9)Cpm and(1 132.2±134.7)Cpm,respectively]compared to the control group[(907.5±76.7)Cpm and(913.0±69.0)Cpm;t=3.528,P=0.024;t=-4.433,P=0.011].A positive correlation was observed between cell viability and radioactive iodine uptake in both the control group and the PBF-shRNA group(r=0.581,P=0.003;r=0.871,P＜0.001).Western blot results showed that silencing PBF protein expression reduced MDM2 protein levels(t=4.630,P=0.001)but increased NIS protein expression in the PBF-shRNA group compared to the control group(t=3.850,P=0.003).Conclusion The reduction in TPC-1 cell viability and the increase in Na131I uptake may be asso-ciated with PBF regulation of differential MDM2 and NIS protein expression.