microRNA-215异常激活抑制Dicer1促进肝癌细胞迁移和转化

Aberrant Activation of MicroRNA-215 Promotes Hepatocellular Carcinoma Cell Migration and Transformation through Directly Inhibiting Dicer1

microRNA异常表达促进癌症的发生发展.本研究通过microRNA表达谱分析2个肝癌细胞和2个正常细胞microRNA的表达,寻找与肝癌相关的microRNA,发现microRNA-215在肝癌细胞中高表达,q RT-PCR验证microRNA-215在肝癌细胞呈显著高表达.进一步研究发现,microRNA-215直接靶向Dicer1基因的3′UTR并抑制Dicer1蛋白表达,Dicer1是microRNA加工成熟过程中必需的蛋白.过表达microRNA-215抑制Dicer1从而促进肝癌细胞迁移和转化,而抑制microRNA-215表达起相反作用.Dicer1抑制后,许多抑癌microRNA表达被抑制,从而促进迁移和转化.相对于癌旁组织,Dicer1在肝癌组织呈明显低表达.本研究揭示,microRNA-215异常活化并抑制Dicer1表达与肝癌发展相关.

Aberrant activation of microRNA contributes to cancer progression. To identify microRNA associated with hepatocellular carcinoma （HCC）, microRNA-215 was found to be upregulated in HCC cells by comparing the global microRNA expression profile of HCC cells to those of normal cells, microRNA-215 was confirmed to display significantly high expression in HCC cells using stem-loop qRT-PCR, microRNA-215 directly inhibits expression of Dicerl which is essential for processing microRNA. Ectopic expression of microRNA-215 promotes migration and transformation while inhibition of its expression has the reverse effects with an associated regulation of microRNA-215 target gene, Dicer1. Inhibition of Dicer1 promotes malignant migration and transformation with an associated reduction of many tumor suppressor microRNAs. Dicer1 displayed significantly lower expression in HCC tissues compared to adjacent normal tissues. Our findings suggest that downregulation of Dicerl by aberrant activation of microRNA-215 is associated with malignant progression of HCC.