CAJ | 학술논문

目的 microRNAs (miRNAs)是内源性非编码小RNA,肿瘤细胞中大多数miRNAs表达降低,探讨miRNAs抑制肿瘤的机制.方法应用实时定量PCR检测非小细胞肺癌组织miR-34b的表达,并且分析其与临床病理参数之间的关系.应用细胞转染技术获得miR-34b高表达细胞,并检测细胞凋亡与细胞增殖.运用免疫组织化学方法探索miR-34b表达与下游蛋白c-Met、p53以及Mdm2之间的相关性.结果 miR-34b在非小细胞肺癌中低表达,并与淋巴结转移负相关(P=O.031).miR-34b通过诱导凋亡抑制肿瘤增殖.非小细胞肺癌中miR-34b表达与c-Met负相关(P=0.012).结论 HGF-Met信号通路中p53磷酸化并增强转录活性,上调miR-34b,反馈抑制c-Met；miR-34b影响肿瘤细胞凋亡、增殖、转移,在肿瘤发展过程中发挥抑制肿瘤的作用.
목적 microRNAs (miRNAs)시내원성비편마소RNA,종류세포중대다수miRNAs표체강저,탐토miRNAs억제종류적궤제.방법 응용실시정량PCR검측비소세포폐암조직miR-34b적표체,병차분석기여림상병리삼수지간적관계.응용세포전염기술획득miR-34b고표체세포,병검측세포조망여세포증식.운용면역조직화학방법탐색miR-34b표체여하유단백c-Met、p53이급Mdm2지간적상관성.결과 miR-34b재비소세포폐암중저표체,병여림파결전이부상관(P=O.031).miR-34b통과유도조망억제종류증식.비소세포폐암중miR-34b표체여c-Met부상관(P=0.012).결론 HGF-Met신호통로중p53린산화병증강전록활성,상조miR-34b,반궤억제c-Met；miR-34b영향종류세포조망、증식、전이,재종류발전과정중발휘억제종류적작용.
Objective Background:MicroRNAs (miRNAs) are naturally occurring small non-coding RNAs,play important roles in cancer initiation and progression.Decreases in miRNAs levels are observed in human cancers,indicating that miRNAs may function intrinsically in tumor suppression.However,the underline mechanisms of miRNA function are little known.Methods MiR-34b in non-small cell lung cancer (NSCLC) tissues was detected using quantitative Real-Time PCR.The relations between miR-34b expression level and clinical pathological parameters were assessed.For in vitro studies,lung cancer cells were transfected with double stranded synthetic miRNA mimics and scrambled controls.Immunohistochemistry technology was explored to validate the related downstream proteins of miR-34b.Results Expression of miR-34b was lower in NSCLC tissues than that in pericarcinous tissues of lung cancer.Additionally,the Spearman correlation test showed lower miR-34b expression was correlated with higher lymph node metastasis (P =0.031).In vitro gain-of-function experiments indicated that miR-34b suppressed cell proliferation by inducing cell apoptosis.IHC results showed relations between lower miR-34b and over-expression of phospho-Met (P =0.012).Conclusion MiR-34b down-regulates Met,following with subsequent changes of downstream p53 and Mdm2,and inversely p53 up-regulates miR-34b in a feedback loop.MiR-34b plays profound roles in progression of NSCLC by inducing apoptosis and decreasing lymph node metastasis.