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微小RNA(miRNA)参与了肿瘤的耐药过程.本研究通过建立对奥沙利铂(oxaliplatin,Oxa)耐药的肝癌细胞系BEL-7402/Oxa和Hep-3B/Oxa,利用miRNA芯片结合实时荧光定量PCR的方法,筛选得到数个参与肝癌细胞对奥沙利铂耐药的miRNA分子,其中miR-93表达增加最为明显.MTT实验发现,增加肝癌细胞株中miR-93的表达可以增强其对奥沙利铂的耐药性.进一步结合生物信息学、荧光报告载体及免疫印迹实验,证实miR-93通过靶定抑癌基因PTEN增加肝癌细胞对奥沙利铂的耐药性.总之,肝癌耐药细胞系的建立及其miRNA差异表达谱的分析,以及miRNA分子对肝癌细胞发生奥沙利铂耐药的具体作用及其分子机制的研究,不仅有助于理解肝癌细胞发生耐药的分子机制,而且为探索克服肝癌对奥沙利铂耐药性的有效途径提供可靠依据.
MicroRNAs (miRNAs) are involved in the tumor resistance process.In this study, we established a hepatoma cell line BEL-7402 / Oxa and Hep-3B / Oxa resistant to oxaliplatin (Oxa) The results of MTT assay showed that increasing the expression of miR-93 in hepatocellular carcinoma cells could enhance the expression of miRNA-93 in hepatocellular carcinoma cells On the resistance of oxaliplatin.Combined with bioinformatics, fluorescence reporter and western blotting, further confirmed that miR-93 can enhance the drug resistance of hepatocarcinoma cells to oxaliplatin by targeting tumor suppressor gene PTEN.In conclusion, The establishment of hepatoma drug resistant cell lines and their miRNA differential expression profiling, as well as the specific role of miRNA molecules in the development of oxaliplatin-resistant hepatocellular carcinoma cells and their molecular mechanisms not only help to understand the occurrence of drug-resistant hepatoma cells Molecular mechanisms, but also provide a reliable basis for exploring effective ways to overcome the drug resistance of liver cancer to oxaliplatin.