ADGRD1抑制非小细胞肺癌细胞增殖和转移的作用及其分子机制  

The mechanism of ADGRD1 inhibits cell proliferation and migration in non⁃small cell lung cancer

作　　者：邓建华 陈瑞 李道生 段训凰[1] DENG Jianhua;CHEN Rui;LI Daosheng;DUAN Xunhuang(Third Department of Oncology,the First People′s Hospital of Jiujiang,Jiangxi Province,Jiujiang 332001,China)

机构地区：[1]九江市第一人民医院肿瘤三科,江西九江332001

出　　处：《实用医学杂志》2023年第5期550-556,共7页The Journal of Practical Medicine

基　　金：江西省卫生健康委科技计划(编号:SKJP220219857)。

摘　　要：目的 探讨黏附G蛋白耦联受体D1(ADGRD1)在非小细胞肺癌(non-small cell lung cancer,NSCLC)的发生发展中的作用及其分子机制。方法 通过肿瘤基因图谱(The Cancer Genome Atlas,TCGA)数据库分析ADGRD1在NSCLC中的表达,以及与NSCLC患者预后的关系;利用定量聚合酶链反应(quantitative polymerase chain reaction,qPCR)检测ADGRD1在肺癌及其癌旁正常组织中的表达;在不同的肺癌细胞系中过表达或敲减ADGRD1后利用CCK-8(Cell Counting Kit-8)、细胞克隆形成和迁移实验分别观察ADGRD1对NSCLC细胞增殖和迁移能力的影响;利用western blot实验检测其下游通路探究ADGRD1发挥作用的潜在机制。结果 TCGA数据库分析结果显示,ADGRD1基因在肺癌组织中的表达明显低于癌旁正常组织(P <0.05),且与患者的不良预后相关(P <0.01);20例临床肺癌样本qPCR结果显示,ADGRD1mRNA水平较其癌旁正常组织显著降低(0.56±0.16 vs. 1.00±0.22,P <0.01);在A549和H1299细胞系中过表达ADGRD1后会明显抑制细胞的增殖(P <0.001)和迁移能力(P <0.01),而在H1975细胞中敲低ADGRD1后会显著促进细胞的增殖(P <0.01)和迁移能力(P <0.001);其机制可能与AKT-mTOR通路密切相关。结论 ADGRD1的表达可以显著抑制NSCLC的增殖和转移,可能成为NSCLC的新的预后诊断和治疗药物靶点。Objective Lung cancer has become one of the main causes of cancer death.Currently,the therapeutic effect of various kinds of lung cancer is limited.It is urgent to continue exploring potential therapeutic targets for lung cancer.This study is to investigate the function and mechanism of ADGRD1 in non⁃small cell lung cancer(NSCLC).Methods Analyzing the expression level of ADGRD1 in NSCLC tissues through The Cancer Genome Atlas(TCGA)database,and the relationship between ADGRD1 expression and the prognosis of NSCLC patients.Quantitative polymerase chain reaction(qPCR)was used to detect the expression of ADGRD1 in lung cancer and its adjacent normal tissues.After ADGRD1 overexpression or knockdown in different lung cancer Cell lines,CCK⁃8(Cell Counting Kit⁃8)and cell clone formation assay were used to observe the effect of ADGRD1 on the proliferation of NSCLC cells.Meanwhile,cell migration assay was used to observe the effect of ADGRD1 on the migration of NSCLC cells.The downstream pathway was detected by western blot to explore the potential mecha⁃nism of ADGRD1.Results TCGA database analysis found that the expression of ADGRD1 in lung cancer tissues was significantly lower than that in adjacent normal tissues(P<0.05),and decreased ADGRD1 expression was associated with poor prognosis(P<0.01).The results of qPCR detection of 20 clinical samples showed that the ADGRD1 mRNA level decreased in lung tumor compared with its adjacent normal tissues(0.56±0.16 vs.1.00±0.22,P<0.01).ADGRD1 Overexpression in A549 and H1299 cells significantly inhibited cell proliferation(P<0.001)and migration(P<0.01),while knockdown of ADGRD1 in H1975 cells significantly promoted cell prolif⁃eration(P<0.01)and migration(P<0.001).The study of functional mechanism shows that ADGRD1 may be closely related to the proliferation and metastasis of lung cancer cells through the AKT⁃mTOR pathway.Conclusions ADGRD1 significantly inhibits the proliferation and metastasis of NSCLC,which may be a novel prognostic diagnostic and therapeutic tar

关 键 词：黏附G蛋白耦联受体D1 非小细胞肺癌 增殖 转移 

分 类 号：R734.2[医药卫生—肿瘤]