N6-甲基腺苷甲基化相关基因IGF2BP3在肾透明细胞癌的作用研究  

Role of N6-methyladenosine methylation related gene IGF2BP3 in renal clear cell carcinoma

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作  者:王咸钟[1] 王忠[1] 何大鹏[1] 赖亚明 安文亚 孙祖刚 谢习颂 吴春香 WANG Xianzhong;WANG Zhong;HE Dapeng;LAI Yaming;AN Wenya;SUN Zugang;XIE Xisong;WU Chunxiang(Department of Urology,Guangyuan Central Hospital,Guangyuan,Sichuan 628000,China;School of Public Health,Wuhan University,Wuhan,Hubei 430070,China)

机构地区:[1]广元市中心医院泌尿外科,四川广元628000 [2]武汉大学公共卫生学院,湖北武汉430070

出  处:《国际检验医学杂志》2025年第1期27-31,共5页International Journal of Laboratory Medicine

基  金:广元市市级科技项目(20ZDYF0021)。

摘  要:目的筛选肾透明细胞癌(ccRCC)中的关键N6-甲基腺苷(m^(6)A)甲基化相关基因,并研究其与ccRCC预后、ccRCC细胞的迁移和侵袭的关系。方法从癌症基因组图谱(TCGA)和基因型组织表达(GTEx)数据库中下载ccRCC和癌旁组织的RNA测序数据和临床数据,采用R4.1.1分析表达谱和预后,并筛选关键基因。收集10例ccRCC手术临床标本,采用定量PCR(qPCR)和免疫组织化学法分别检测基因mRNA和蛋白表达。在人ccRCC细胞系RCC23中,通过SiRNA敲减关键基因,并用CCK-8检测细胞的存活率,采用划痕试验和Transwell试验分别检测细胞的迁移和侵袭。结果19个m^(6)A甲基化相关基因中仅有胰岛素样生长因子ⅡmRNA结合蛋白3(IGF2BP3)在ccRCC组织中高表达,且IGF2BP3高表达与ccRCC患者预后不良呈正相关。通过qPCR和免疫组织化学法在临床标本中验证了IGF2BP3的高表达。通过小干扰RNA(siRNA)将IGF2BP3敲减后发现,RCC23细胞的存活率明显下降,且细胞的迁移和侵袭能力下降。结论IGF2BP3可能是预测ccRCC患者预后的生物标志物和潜在的药物治疗靶点。Objective To screen the key N6-methyladenosine(m^(6)A)methylation related genes in renal clear cell carcinoma(ccRCC),and to study their expression and relationship with the prognosis,migration and invasion of renal clear cell carcinoma.Methods The RNA sequencing data and clinical data of ccRCC and adjacent tissues were downloaded from the Cancer Genome Atlas(TCGA)and GTEx(Genotype-Tissue Expression).The expression profile and prognosis were analyzed with R 4.1.1,and the key genes were screened.Clinical specimens of 10 patients with ccRCC were collected.The mRNA and protein expressions were detected by RT-qPCR and immunohistochemistry,respectively.In human ccRCC cell line RCC23,siRNA was used to knock down key genes,and CCK-8 was used to detect the survival rate of cells.Scratch test and Trans well test were used to detect the migration and invasion of cells,respectively.Results Among the 19 m^(6)A methylation related genes,only insulin-like growth factor 2 mRNA binding protein 3(IGF2BP3)was highly expressed in cancer tissues,and the high expression was significantly positively correlated with poor prognosis.The high expression of IGF2BP3 was verified in clinical specimens by RT-qPCR and immunohistochemistry.After knockdown of IGF2BP3 by siRNA,the survival rate of RCC23 cells decreased significantly,and the migration and invasion ability of cut cells decreased.Conclusion These results suggest that IGF2BP3 may be an effective biomarker and potential drug target for predicting the prognosis of patients with ccRCC.

关 键 词:肾透明细胞癌 N6-甲基腺苷甲基化 胰岛素样生长因子ⅡmRNA结合蛋白3 迁移 侵袭 

分 类 号:R737.11[医药卫生—肿瘤]

 

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