Sufu突变通过调控Gli1促进肺腺癌恶性进展  

Sufu mutation promotes malignant progression of lung adenocarcinoma by regulating Gli1

作　　者：刘继宏 罗虎 衣杏林 周向东 LIU Jihong;LUO Hu;YI Xinglin;ZHOU Xiangdong(Department of Pulmonary and Critical Care Medicine,First Affiliated Hospital,Army Medical University(Third Military Medical University),Chongqing,400038,China)

机构地区：[1]陆军军医大学(第三军医大学)第一附属医院呼吸与危重症医学科,重庆400038

出　　处：《陆军军医大学学报》2024年第10期1142-1149,共8页Journal of Army Medical University

摘　　要：目的观察Sufu在肺腺癌中的突变情况以及Sufu突变后对Gli1转录调控的变化,探讨Sufu对肺腺癌进展的作用。方法通过cBioPortal网站获取Sufu在肺癌中的突变情况;构建4个Sufu单碱基突变载体;在肺腺癌细胞株(A549和H1975)中分别对Sufu进行过表达和敲除;通过细胞划痕实验检测Sufu对肺腺癌细胞迁移能力的影响;通过RT-qPCR、细胞免疫荧光和双荧光素酶报告基因实验观测Sufu突变后对Gli1转录水平的影响。结果cBioPortal网站数据显示:Sufu在肺腺癌中突变率分别为11.76%(肺鳞癌:2/17)、0.96%(肺腺癌:6/625)、1.01%(小细胞肺癌:4/396)和0.69%(非小细胞肺癌:77/11227);Sufu发生突变后,肺癌患者中位生存期显著降低[54.34(未突变组)vs 38.00(突变组)个月,HR=1.943,P<0.05];A549细胞对Sufu敲除敏感,能显著上调Gli1的转录水平(P<0.05);在A549和H1975中,过表达Sufu能抑制细胞迁移(P<0.05);Sufu突变后,Gli1细胞定位未发生明显改变;Sufu-T411M突变能上调Gli1的转录水平(P<0.05)。结论Sufu对肺腺癌转移有抑制作用,Sufu具有成为肺腺癌转移治疗靶点的潜力。Objective To explore the effect of Sufu on lung adenocarcinoma by observing its mutation and the changes in Gli1 transcription after its mutation.Methods cBioPortal for Cancer Genomics was used to obtain the mutation status of Sufu in lung cancer.Four Sufu single base mutation vectors were constructed and transfected into lung adenocarcinoma cell lines A549 and H1975 to establish cells with Sufu overexpression and knockout.Wounding healing assay was employed to determine the effect of Sufu on cell migration,and RT-qPCR,immunofluorescence assay and dual luciferase reporter gene assay were utilized to explore the changes in Gli1 transcription after Sufu mutation.Results cBioPortal data showed that the mutation rate of Sufu in lung cancer was 11.76%in squamous cell carcinoma(2/17),0.96%in adenocarcinoma(6/625),1.01%in small cell lung cancer(4/396),and 0.69%in non-small cell lung cancer(77/11227).The median survival of lung cancer patients was significantly decreased in those with Sufu mutation than those without(38.00 vs 54.34 months,HR=1.943,P<0.05).A549 cells were sensitive to Sufu knockout,and it resulted in significant increase of the transcription level of Gli1(P<0.05).Overexpression of Sufu inhibited cell migration ability in both A549 and H1975 cells(P<0.05).Sufu mutation had no significant influence on the location of Gli1 in the cells.The Sufu-T411M mutation up-regulated the the transcription level of Gli1(P<0.05).Conclusion Sufu has an inhibitory effect on lung adenocarcinoma metastasis,and can be regarded as a potential target for lung adenocarcinoma metastasis.

关 键 词：肺腺癌 HEDGEHOG信号通路 SUFU GLI1 

分 类 号：R394.3[医药卫生—医学遗传学] R730.23[医药卫生—基础医学] R734.2