LncRNA IGF2-AS表达上调促进结直肠癌的进展  

Up-regulation of lncRNA IGF2-AS expression promotes progression of colorectal cancer

作　　者：崔丽娇 吴秀 顾志伟 周宇 喻才元 CUI Lijiao;WU Xiu;GU Zhiwei;ZHOU Yu;YU Caiyuan(Department of Gastroenterology,the Affiliated Hospital of Guangdong Medical University,Zhanjiang 524001;Guangdong Medical University,Zhanjiang 524023,China)

机构地区：[1]广东医科大学附属医院消化内科,广东湛江524001 [2]广东医科大学,广东湛江524023

出　　处：《基础医学与临床》2025年第3期323-330,共8页Basic and Clinical Medicine

基　　金：广东医科大学科研基金(GDMUM2020010,GDMUM2020013);广东省医学科学技术研究基金(B2023050);湛江市科技攻关计划(2020B01353);广东省自然科学基金(2023A1515010530)。

摘　　要：目的了解lncRNA IGF2-AS在结直肠癌中的表达及临床意义;验证胰岛素样生长因子2反义链(IGF2-AS)在细胞中的生物学功能;筛选受IGF2-AS调控的蛋白分子。方法利用生物信息学预测IGF2-AS在结直肠癌中的表达和临床意义;运用RT-qPCR检测IGF2-AS mRNA的表达;运用小干扰RNA敲低IGF2-AS;运用CCK8法、Transwell小室法和流式细胞测量术分别检测细胞的增殖、迁移和凋亡;利用Label-free定量蛋白质组学筛选受IGF2-AS调控的相关因子;运用GenCards、OMIM、TTD等数据库结合蛋白质组学结果筛选出结直肠癌中受IGF2-AS调控的核心靶点。结果生物信息分析表明,IGF2-AS在结直肠癌中显著上调(P<0.001),且其表达可能与肿瘤TNM分期(P<0.01)及有无淋巴结转移(P<0.001)相关;RT-qPCR结果表明,与对照组相比IGF2-AS mRNA在结直肠癌组织和大多数结肠癌细胞中的表达显著上调(P<0.01);临床资料表明,IGF2-AS的表达可能与淋巴结转移(P<0.05)相关;生物学功能实验结果表明,IGF2-AS siRNA转染组结直肠癌细胞增殖率及迁移率均显著减低(P<0.0001),凋亡率显著增加(P<0.05);KRAS、TCF7L2、CASP3等13个蛋白可能是受IGF2-AS调控的核心靶点。结论IGF2-AS在结直肠癌中表达显著上调,可能发挥促癌作用。Objective To investigate the expression and clinical significance of lncRNA insulin growth factor 2 antisense IGF2-AS in colorectal cancer;To verify the biological function of IGF2-AS in cells and to screen protein molecules regulated by IGF2-AS.Methods Using bioinformatics to predict the expression and clinical significance of IGF2-AS in colorectal cancer;Using RT-qPCR to detect the expression of IGF2-AS mRNA;Using small interfering RNA to knockdown IGF2-AS;Using CCK8,Transwell assay and flow cytometry to detect proliferation,migration,and apoptosis,respectively;Using label free quantitative proteomics to screen for factors regulated by IGF2-AS;Using databases such as GenCards,OMIM,TTD,and proteomics results screening for core targets regulated by IGF2-AS in colorectal cancer.Results Bioinformatics analysis showed that IGF2-AS was significantly upregulated in colorectal cancer(P<0.001),its expression might be related to TNM stage(P<0.01)and the presence of lymph node metastasis(P<0.001);RT-qPCR results showed that as compared to the control group,the expression level of IGF2-AS mRNA was significantly up-regulated in colorectal cancer tissues(P<0.01)and most colon cancer cells(P<0.0001);Clinical pathological data indicated that the expression of IGF2-AS was potentially associated with the lymph node metastasis(P<0.05);The proliferation rate and migration rate of colorectal cancer cells transfected with IGF2-AS siRNA were significantly reduced(P<0.0001),and the apoptosis rate was significantly increased(P<0.05);There were 13 proteins including KRAS,TCF7L2 and CASP3,that were potentially core targets regulated by IGF2-AS.Conclusions IGF2-AS is significantly up-regulated in colorectal cancer and may play a cancer promoting role in colorectal cancer development.

关 键 词：结直肠癌 长链非编码RNA 胰岛素样生长因子2反义链(IGF2-AS) 

分 类 号：R574.6[医药卫生—消化系统]