lncRNA H19对结肠癌预后评估及辐射抗性的调控作用研究  

The role of lncRNA H19 in prognostic evaluation and regulating the radioresistance in colon cancer

作　　者：李林莹 王江涛 程伟 李强[1,2] 金晓东 Li Linying;Wang Jiangtao;Cheng Wei;Li Qiang;Jin Xiaodong(Institute of Modern Physics,Chinese Academy of Sciences/Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences/Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine,Lanzhou 730000,China;University of Chinese Academy of Sciences,Beijing 100049,China;The First School of Clinical Medicine of Lanzhou University,Lanzhou 730000,China)

机构地区：[1]中国科学院近代物理研究所/中国科学院重离子束辐射生物医学重点实验室/甘肃省重离子束辐射医学应用基础重点实验室,兰州730000 [2]中国科学院大学,北京100049 [3]兰州大学第一临床医学院,兰州730000

出　　处：《中华放射肿瘤学杂志》2022年第12期1153-1159,共7页Chinese Journal of Radiation Oncology

基　　金：国家重点研发计划(2018YFC0115700,2018YFC0115702);国家自然科学基金(11875299,U1532264);中科院重点部署项目(KFZD-SW-222)。

摘　　要：目的探索lncRNA H19在结肠癌预后评估及辐射抗性调控中的作用,为结肠癌的诊疗提供新的潜在靶点。方法基于生物信息学技术分析lncRNA H19在结肠癌临床病理参数及预后评估中的价值。通过siRNA和过表达质粒转染调节lncRNA H19在结肠癌细胞HCT116及SW620中的表达。通过CCK8、EdU、克隆存活及流式细胞术检测调节lncRNA H19表达对X线辐射后结肠癌细胞增殖、DNA合成、辐射敏感性及细胞周期的影响。结果lncRNA H19在结肠癌组织中表达显著上调并与结肠癌患者的预后不良相关。lncRNA H19作为结肠癌的高风险因子,对于结肠癌的预后评估具有显著的优势(曲线下面积值为0.816)。进一步的实验表明,辐射可以诱导lncRNA H19在结肠癌细胞中高表达。敲低lncRNA H19(siRNA-H19)可以明显增加HCT116细胞对X线的敏感性,而过表达lncRNA H19(H19-OE)的SW620细胞辐射抗性增强。此外,流式分析显示敲低lncRNA H19可以增强X线诱导的G2/M期阻滞,提示lncRNA H19可能通过参与细胞周期调控影响结肠癌细胞的辐射敏感性。结论lncRNA H19在结肠癌预后评估及辐射抗性调控中发挥关键作用,可能作为增强放疗敏感性的潜在靶点。Objective To investigate the role of lncRNA H19 in evaluating prognosis and regulating radioresistance of colon cancer,aiming to provide a new potential target for the diagnosis and treatment of colon cancer.Methods The value of lncRNA H19 in the clinicopathological parameters and prognosis of colon cancer was assessed based on bioinformatics technology.The expression of lncRNA H19 in HCT116 and SW620 cells was regulated through siRNA and overexpression plasmid transfection,respectively.The effect of regulating lncRNA H19 expression on the proliferation,DNA synthesis,radiosensitivity and cell cycle of colon cancer cells after X‐ray irradiation were detected by CCK8,EdU,cell clonogenic survival assay and flow cytometry.Results The expression of lncRNA H19 was significantly upregulated in colon cancer tissues and correlated with poor prognosis in colon cancer patients.LncRNA H19,as a high‐risk gene for colon cancer,had a significant advantage for prognostic assessment of colon cancer(AUC=0.816).Furthermore,the expression of lncRNA H19 was upregulated after X‐ray irradiation in colon cancer cells.Knockdown of lncRNA H19(siRNA‐H19)significantly increased the radiosensitivity in HCT116 cells,while overexpression of lncRNA H19(H19‐OE)enhanced the radioresistance in SW620 cells.Moreover,flow cytometry revealed that the G2/M phase arrest induced by X‐ray irradiation was obviously aggravated after siRNA‐H19 treatment in colon cancer cells,which suggested that lncRNA H19 might regulate the radiosensitivity by inhibiting cell cycle progression.Conclusion LncRNA H19 plays a key role in the prognostic assessment and regulating the radiosensitivity in colon cancer,which can be used as a potential target for improving radiosensitivity of colon cancer radiotherapy.

关 键 词：结肠肿瘤 辐射抗性 lncRNA H19 预后 细胞周期 

分 类 号：R735.35[医药卫生—肿瘤]