miR-204在非小细胞肺癌患者中的表达及其对SIRT1的靶向调控作用

Expression of miR-204 in non-small cell lung cancer and its targeted regulation on SIRT1

目的研究miR-204在非小细胞肺癌(NSCLC)患者中表达的临床意义及其对SIRT1的靶向调控作用。方法收集39例原发性NSCLC患者的癌组织和对应癌旁组织标本。实时荧光定量PCR检测组织标本中miR-204的表达水平;并分析其与NSCLC临床病理学特征的关系。将人非小细胞肺癌细胞株A549分别转染miR-204的模拟物或抑制物,CCK-8试剂盒检测细胞的增殖,western blot检测其潜在靶点基因SIRT1的表达。结果癌组织中miR-204的表达量为(2.12±1.17),明显低于癌旁组织中的(3.08±1.46),P<0.01。miR-204的表达水平与肿瘤的临床分期以及肿瘤大小有关(均P<0.05),但与患者年龄、性别、吸烟史、分化程度、组织类型及淋巴转移情况无关(P>0.05)。A549细胞转染miR-204的抑制物后,细胞的增殖明显增强,SIRT1的表达上调;而转染miR-204模拟物则呈反向变化。结论 miR-204在NSCLC组织中呈低表达,并与患者的临床分期以及肿瘤大小有相关,其可能是通过靶向调控SIRT1而在NSCLC的发生发展中起重要作用。

Objective To investigate the expressions of miR-204 in non small cell lung cancer （NSCLC） and their relations with clinical features and its targeted regulation on SIRT1. Methods The cancer tissues and matched paracancerous tissues were collected from 39 cases with primary NSCLC. Real time RT-PCR was used to detect the expression ofmiR-204 in tissues samples. The relationship between miR-204 expression level and clinicopathologic feature was analyzed too. Human lung cancer A549 cells were transfected with miR-204 mimics or inhibitors, and cell proliferation was analyzed by CCK-8 assay kit and the expression of SIRT 1 was determined by Western blot. Results The relative expression of miR-204 in cancer tissues （2.12-F1.17） was significantly lower than that in paracancerous tissues （3.08_1.46） （P〈0.01）. The miR-204 expression level was closely correlated with tumor size and clinic staging of tumor （P〈0.05 for all）, but have no correlation with the age and gender, smoking history, tissue type, differentiation degree and lymph node metastasis （P〉0.05 for all）. The proliferation was significantly enhanced and SIRT1 protein expression was significantly increased in A549 cells transfected with miR-204 inhibitors, but A549 cells those transfected with miR-204 mimics showed the opposite change. Conclusion miR-204 may play an important role in the incidence and development of NSCLC and can be served as an indicator for the malignancy and outcome assessment of NSCLC.