ARHGEF19在甲状腺乳头状癌侵袭转移中的作用研究  

Effect of ARHGEF19 on Invasion and Metastasis of Papillary Thyroid Cancer

作　　者：吴铃 鲍峰[2] 古仕明[1] 于颖娟[2] WU Ling;BAO Feng;GU Shi-ming;YU Ying-juan(Sichuan College of Traditional Chinese Medicine,Mianyang 621000,China;Mianyang Central Hospital,Mianyang 621000,China)

机构地区：[1]四川中医药高等专科学校,四川绵阳621000 [2]绵阳市中心医院,四川绵阳621000

出　　处：《肿瘤学杂志》2023年第3期208-215,共8页Journal of Chinese Oncology

基　　金：四川省卫生健康科研基金项目(20210914)。

摘　　要：[目的]探讨Rho鸟嘌呤核苷酸交换因子19(ARHGEF19)在甲状腺乳头状癌(papillary thyroid cancer,PTC)侵袭转移中的作用机制。[方法]收集2019年1月至2021年6月诊断为PTC的185例组织样本。采用实时定量PCR、蛋白质印迹和免疫组织化学分析组织中ARHGEF19表达,并评估ARHGEF19表达的临床意义。体外实验选择两种PTC细胞系(TPC-1和KTC-1)用于功能验证。通过Transwell分析和CCK-8分析评估细胞迁移、侵袭和增殖。[结果]在mRNA和蛋白水平上,PTC组织中ARHGEF19的表达水平高于正常甲状腺组织。不同T分期、N分期和TNM分期ARHGEF19高表达占比差异有统计学意义(χ^(2)=6.552、7.074、10.552,P=0.010、0.008、0.001)。ARHGEF19过表达显著性促进KTC-1细胞增殖、迁移和侵袭(t=38.561、18.750、21.302,P均<0.001),而ARHGEF19敲除显著性抑制TPC-1细胞增殖、迁移和侵袭(t=41.266、19.834、23.517,P均<0.001)。此外,与载体组相比,ARHGEF19 OE组KTC-1细胞衍生肿瘤的生长体积和重量显著性增加(P<0.05),并且荷瘤小鼠的总生存期缩短(P<0.05)。[结论] ARHGEF19在PTC中高度表达,并且ARHGEF19通过PTC细胞中的MEK/ERK信号通路发挥致癌作用。[Objective]To investigate the effect and mechanism of Rho guanine nucleotide exchange factor 19(ARHGEF19)on invasion and metastasis of papillary thyroid carcinoma(PTC).[Methods]A total of 185 tissue samples of PTC were collected from Mianyang Central Hospital from January 2019 to June 2021.The mRNA and protein expression of ARHGEF19 in the tissue samples was analyzed by real-time quantitative PCR,Western blotting and immunohistochemistry,respectively.The clinical significance of ARHGEF19 expression was evaluated.Two PTC cell lines,TPC-1 and KTC-1,were employed for functional verification.Cell migration,invasion and proliferation were assessed by Transwell analysis and CCK-8 analysis,respectively.[Results]At the mRNA and protein levels,the expression of ARHGEF19 in PTC tissues was significantly higher than that in normal thyroid tissues.The high expression level of ARHGEF19 was significantly correlated with T stage,N stage and TNM stage(χ^(2)=6.552,7.074,10.552,P=0.010,0.008,0.001).ARHGEF19 overexpression significantly promoted KTC-1 cell proliferation,migration and invasion(t=38.561,18.750,21.302,all P<0.001),while ARHGEF19 knockout significantly inhibited TPC-1 cell proliferation,migration and invasion(t=41.266,19.834,23.517,all P<0.001).In animal experiments,the growth volume and weight of transplanted tumor in mice inoculated with ARHGEF19-overexpressing KTC-1 cells(ARHGEF19 OE group)were significantly increased compared with the vehicle group(P<0.05),and the overall survival of tumor-bearing mice was decreased(P<0.05).[Conclusion]ARHGEF19 is highly expressed in PTC,and ARHGEF19 exerts oncogenic effects through the MEK/ERK signaling pathway in PTC cells.

关 键 词：Rho鸟嘌呤核苷酸交换因子19 甲状腺乳头状癌 侵袭转移 MEK/ERK信号通路 

分 类 号：R736.1[医药卫生—肿瘤]