基础医学与临床 ›› 2025, Vol. 45 ›› Issue (3): 323-330.doi: 10.16352/j.issn.1001-6325.2025.03.0323

• 研究论文 • 上一篇    下一篇

LncRNA IGF2-AS表达上调促进结直肠癌的进展

崔丽娇1, 吴秀1, 顾志伟1, 周宇1,2*, 喻才元1*   

  1. 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
  • 收稿日期:2024-08-27 修回日期:2024-10-30 发布日期:2025-02-25
  • 通讯作者: *gdmcycy2013@126.com;ahdg2022@gdmu.edu.cn
  • 基金资助:
    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)

Up-regulation of lncRNA IGF2-ASexpression promotes progression of colorectal cancer

CUI Lijiao1, WU Xiu1, GU Zhiwei1, ZHOU Yu1,2*, YU Caiyuan1*   

  1. 1. Department of Gastroenterology, the Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001;
    2. Guangdong Medical University, Zhanjiang 524023, China
  • Received:2024-08-27 Revised:2024-10-30 Published:2025-02-25

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<0.000 1),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。

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)

Abstract: 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 expressionlevel of IGF2-AS mRNA was significantly up-regulated in colorectal cancer tissues (P<0.01) and most colon cancer cells(P<0.000 1); 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<0.000 1), 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.

Key words: colorectal cancer, long non-coding RNA, insulin like growth factor 2 antisense(IGF2-AS)

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