利用TCGA数据库分析miR-196b在结直肠癌患者中的临床表达特征并探索miR-196b的体外抗5-FU作用

摘要

目的:研究微小RNA(miR)-196b在结直肠癌患者中的表达及其临床意义,探讨过表达miR-196b的结直肠癌细胞对5-氟尿嘧啶(5-FU)的敏感性.方法:在癌症基因组图谱(The Cancer Genome Atlas,TCGA)公共数据库下载结直肠癌患者miRNA测序数据及其对应的临床病理资料,运用SPSS 17.0分析miR-196b在结直肠癌患者中的表达水平以及临床特征;采用瞬时转染的方法在人结直肠癌HCT116细胞中过表达miR-196b,并用MTS法分析过表达miR-196b的细胞对5-FU药物敏感性的变化.结果:miR-196b高表达与结直肠癌患者淋巴结转移及TNM分期相关(P<0.05),与年龄和性别等无相关性.淋巴结转移和远处转移是直肠癌患者生存的独立影响因子(P<0.05),miR-196b的表达水平与患者生存状况无关.过表达miR-196b的HCT116细胞在不同浓度的5-FU作用下,细胞存活率均明显高于对照组(P<0.05).结论:miR-196b可能是结直肠癌患者肿瘤分期和淋巴结转移的分子标志物,并可降低结直肠癌细胞对5-FU的敏感性.%AIM:To investigate the clinical characteristics of microRNA(miR)-196b in colorectal cancer(CRC)and to study its biological function in 5-fluorouracil(5-FU)resistance.METHODS:miRNA sequence dataset and the corresponding clinical data of CRC patients were downloaded from The Cancer Genome Atlas(TCGA).Expression level and clinical characteristics of miR-196b in CRC patients were analyzed using SPSS 17.0.CRC cell line overexpres-sing miR-196b was established using transient transfection method.MTS test was used to evaluate the effect of miR-196b overexpression on 5-FU resistance.RESULTS:miR-196b expression was associated with lymph node metastasis and TNM stage(P<0.05),but not related with age and sex.Lymph node metastasis and distant metastasis were independent prog-nostic factors for rectal patients(P<0.05).The expression level of miR-196b was not associated with survival condition of rectal patients.The viability of the cells overexpressing miR-196b treated with different concentrations of 5-FU was signifi-cantly higher than that in control group(P<0.05).CONCLUSION:miR-196b may be a potential biomarker of TNM stage and lymph node metastasis in CRC.miR-196b increases the 5-FU resistance of CRC cells.