林小华,江其生,吕进,高俊,段影,王思念,宋秀军,于慧杰,陈火明.电离辐射对肺癌A549细胞miR-21体内外表达的影响及意义[J].中华放射医学与防护杂志,2018,38(3):168-173
电离辐射对肺癌A549细胞miR-21体内外表达的影响及意义
Effects of ionizing radiation on the miR-21 expression in A549 cells in vitro and in vivo
投稿时间:2017-12-14  
DOI:10.3760/cma.j.issn.0254-5098.2018.03.002
中文关键词:  miR-21  电离辐射  miRNA  肺癌  A549细胞
英文关键词:miR-21  Irradiation  miRNA  Lung cancer  A549 cell
基金项目:国家自然科学基金(31770914);军队后勤重大科研项目(AEP17J001)
作者单位E-mail
林小华 121000 锦州医科大学火箭军总医院研究生培养基地  
江其生 100088 北京, 火箭军总医院核与辐射损伤实验室  
吕进 100088 北京, 火箭军总医院核与辐射损伤实验室  
高俊 100088 北京, 火箭军总医院核与辐射损伤实验室  
段影 100088 北京, 火箭军总医院放疗科  
王思念 100088 北京, 火箭军总医院核与辐射损伤实验室  
宋秀军 100088 北京, 火箭军总医院核与辐射损伤实验室  
于慧杰 100088 北京, 火箭军总医院核与辐射损伤实验室  
陈火明 100088 北京, 火箭军总医院肿瘤科 chenhuoming1881@sina.com 
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中文摘要:
      目的 研究miR-21在肺癌组织及血清中的表达与肺癌预后及放疗因素的关系,进而探讨电离辐射对人肺癌A549细胞体内外表达miR-21的影响。方法 收集肺癌患者病理组织及血清样本,检测不同病理类型肺癌组织及血清中的miR-21的表达水平,同时检测是否接受放疗的非小细胞肺癌患者血清中miR-21的表达水平,并进行生存分析;以2、4 Gy X射线照射体外培养的A549细胞,并以A549细胞制备裸鼠肺转移癌模型,分别检测A549细胞与裸鼠血清及肺中miR-21的表达水平。结果 肺癌组织中miR-21高表达占60.0%;肺癌血清中miR-21高表达占50.5%,腺癌与鳞癌检出率差异有统计学意义(χ2=5.766,P<0.05);87例非小细胞肺癌中放疗患者miR-21检出率66.7%显著高于非放疗患者39.6%(χ2=6.321,P<0.05);Kaplan-Meier法生存分析显示,miR-21高表达患者预后明显低于低表达患者,差异有统计学意义(P<0.05);Cox回归模型分析显示,miR-21高表达、区域淋巴结转移及放疗均为影响患者预后的独立危险因素。2、4 Gy X射线照射A549细胞后不同时间点miR-21表达显著升高(t=-7.552~-1.206,P<0.05),miR-21在裸鼠血清及肺组织中的表达水平显著升高(t=-47.845~-2.356,P<0.05)。结论 电离辐射可上调A549细胞体内外miR-21的表达水平,可能与增强A549细胞侵袭转移能力相关。
英文摘要:
      Objective To investigate the expressions of miR-21 in clinical lung tissues, serum of lung cancer patients and X-ray irradiated A549 cells in vitro and in vivo. Methods A549 cells were irradiated with 2 and 4 Gy X-rays, and pulmonary metastasis model of lung cancer in nude mice was established to detect the expression of miR-21 in vitro and in vivo,as well as in clinical lung tissues of different pathological types serum sample of lung cancer patients and NSCLC patients whether or not received radiotherapy. The survival rate was further analyzed in the above mention NSCLC patients. Results The miR-21 expressions was up-regulated in 60.0% of tissue samples of NSCLC patients, and it was up-regulated in 50.5% serum samples of lung cancer patients (52 out of 103). The miR-21 expressions in lung adenocarcinoma and squamous cell carcinoma had significant difference (χ2=5.766, P<0.05). In the serum samples of 87 NSCLC patients, miR-21 was detected in 66.7% samples from the patients of radiotherapy but only 39.6% of patients without radiotherapy (χ2=6.321, P<0.05). Kaplan-Meier curves showed that the survival rate of patients with low miR-21 expression was higher than that with high miR-21 expression (P<0.05). Multivariate Cox regression analysis demonstrated that the miR-21 expression, regional lymph node metastasis and radiotherapy were independent prognostic factors for NSCLC patients. The expression of miR-21 was up-regulated significantly in X-ray irradiated A549 cells at different time-points after irradiation (t=-7.552--1.206, P<0.05). Furthermore, the expression of miR-21was up-regulated in the serum and lung of nude mice (t=-47.845--2.356, P<0.05). Conclusions The X-ray irradiation could up-regulate the expression of miR-21 in A549 cells in vitro and in vivo, which might be correlated with the enhanced metastasis of A549 cells.
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