双链嵌合microRNA用于治疗肝细胞癌的研究

项目名称： 双链嵌合microRNA用于治疗肝细胞癌的研究

项目编号： No.81502670

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 张翔

作者单位： 中国人民解放军第四军医大学

项目金额： 18.5万元

中文摘要： 联合使用多种microRNA(miRNA)用于肝癌的生物治疗是目前较新的研究策略，但存在联用后效率不高和miRNA*(sense链)作用不明等问题。miRNA主要是通过其5’端2-8位碱基（种子区）发挥抑制靶mRNA翻译作用的。大量工作证实，miR-26a和miR-101是抑制肝癌的miRNA。因此，我们选其各自包含种子区的一半（包括互补序列）进行反向拼接，组成一种两条链均为antisense链的嵌合miRNA。前期试验提示，单独使用该嵌合miRNA便能起到大于miR-26a和miR-101加合的作用，且不存在sense链的干扰。因此，嵌合miRNA可能是提高治疗效率并减少不明靶基因的理想方案。本课题拟通过细胞和动物水平实验，比较使用嵌合miRNA和单独或联合使用miR-26a、miR-101对肝癌恶性表型的抑制效率。本研究具有扩展miRNA治疗策略的理论意义，并对肝癌的治疗具有实际意义。

中文关键词： 双链；嵌合微小RNA；肝细胞癌

英文摘要： It is a promising strategy to treat hepatocellular carcinoma (HCC) with compound microRNAs (miRNAs). However, this strategy still has some shortcomings, such as low efficiency of mature miRNAs and inconclusive side effect of miRNA*(the sense strand). It is widely accepted that miRNAs are posttranscriptional regulators of gene expression through directly degrading messenger RNA (mRNA) or indirectly repressing protein translation. This effect is based on complementary base paring between seed sequence region in miRNA and seed sequence region binding sites in mRNA. Since miR-26a and miR-101 are reported as HCC suppressor miRNAs, we created a kind of double-strand chimeric miRNA (CM) containing seed sequence regions of both miR-26a and miR-101. Then, we compared the suppression effect on known target genes among this CM and natural miRNAs. It was found that this CM could play more powerful role than both miR-26a and miR-101. Thus, CM might be a better strategy to treat cancers. In this study, we are eager for comparing the tumor suppression effect between the CM and natural miRNAs in vitro and in vivo. This study will not only extend the miRNA therapautic strategy in theory, but also have practical significance in the treatment of HCC.

英文关键词： double-strand;chimeric microRNA;hepatocellular carcinoma