小整合膜蛋白22在肺癌恶性进展中的作用机制研究  

Study on the mechanism of small integral membrane protein 22 in the malignant progression of lung cancer

作　　者：闫红江[1] 焦晓丹[2] 王保华[1] 李书军[1] 张合林[1] 方艳伟[3] YAN Hongjiang;JIAO Xiaodan;WANG Baohua;LI Shujun;ZHANG Helin;FANG Yanwei(Department of Thoracic Surgery,the Second Hospital of Hebei Medical University,Shijiazhuang 050051,China;Department of Respiratory Medicine,the Second Hospital of Hebei Medical University,Shijiazhuang 050051,China;Department of Emergency,the Second Hospital of Hebei Medical University,Shijiazhuang 050051,China)

机构地区：[1]河北医科大学第二医院胸外科,河北石家庄050051 [2]河北医科大学第二医院呼吸内科,河北石家庄050051 [3]河北医科大学第二医院急诊科,河北石家庄050051

出　　处：《安徽医学》2023年第7期762-766,共5页Anhui Medical Journal

基　　金：河北省医学科学研究课题计划(编号:20210982)。

摘　　要：目的探讨小整合膜蛋白22(SMIM22)在肺癌恶性进展中的作用及分子机制。方法使用TCGA数据库获取SMIM22在肺癌组织中的表达水平;在H1299和H1975细胞中干扰SMIM22基因表达,定量聚合酶链反应(qPCR)观察其干扰效果并用CCK8检测干扰对肺癌细胞增殖的影响、流式细胞术检测干扰肺癌细胞凋亡和周期的影响;蛋白免疫印迹(Western Blot)检测干扰SMIM22对H1299细胞中p-MEK、MEK和c-myc蛋白水平的影响;qPCR检测干扰SMIM22对c-myc下游基因Cyclin D2、Cyclin E1、CDK2和CDK4的mRNA表达的影响。结果与癌旁组织相比,SMIM22在肺癌组织中表达升高(P<0.05);SMIM22高表达与肺癌患者不良预后相关。SMIM22表达降低,能抑制肺腺癌细胞增殖、促进细胞凋亡并将细胞周期阻滞在G0/G1期。敲低SMIM22后,与MEK-MYC通路相关的蛋白(如p-MEK、c-MYC)表达水平降低,相关基因(如Cyclin D2、Cyclin E1、CDK2、CDK4)表达水平也降低(P<0.05)。结论SMIM22在肺癌组织中高表达,通过调控MEK-MYC通路参与肺癌的恶性发展,可能成为肺癌新的潜在诊断指标及治疗靶点。Objective To investigate the function and mechanism of small integrated membrane protein 22(SMIM22)in malignant pro-gression of lung cancer.Methods First,TCGA database was used to obtain the expression level of SMIM22 in lung cancer tissue.Then the ef-fects of SMIM22 on the proliferation,apoptosis and cycle of lung cancer cells were observed in H1299 and H1975 cells.The effect of interfer-ence was observed by qPCR and the effect on lung cancer cell proliferation was assessed by CCK 8,and that on lung cancer cell apoptosis and cycle was evaluated by flow cytometry.The effect of interfering SMIM22 on the levels of p-MEK,MEK and c-myc protein in H1299 cells was detected by Western blot.The effect of interfering SMIM22 on the mRNA expression of c-myc downstream genes Cyclin D2,Cyclin E1,CDK 2 and CDK 4 was determined by qPCR.Results Compared with the adjacent tissues,the expression of SMIM22 was higher in lung cancer tis-sue(P<0.05)and was related to the poor prognosis of patients.The decreased expression of SMIM22 inhibited lung cancer cell proliferation,promoted cell apoptosis and blocked the cell cycle at G0/G1 phase.After knocking down SMIM22,the expression level of proteins related to MEK-MYC pathway(such as p-MEK,c-MYC)decreased,and the expression level of related genes(such as Cyclin D2,Cyclin E1,CDK2,CDK4)also decreased significantly(P<0.01).Conclusion SMIM22 ws highly expressed in lung cancer tissue and participates in the malig-nant development of lung cancer by regulating the MEK-MYC pathway,which may become a new potential diagnostic index and therapeutic target for lung cancer.

关 键 词：小整合膜蛋白22 肺癌 丝裂原活化的细胞外信号调节激酶-细胞致瘤基因通路 

分 类 号：R73[医药卫生—肿瘤]