miRNA通过转录或者转录后抑制或激活等多种方式调控基因表达。人IGF-II基因内含子来源的miR-483-5p（以下简称5p）与多种恶性肿瘤的发生及预后密切相关，但是该miRNA在肝细胞癌（HCC）中的具体作用还不清楚。我们前期研究发现，在肝癌细胞中，5p靶向IGF-II基因的转录本之一P3 mRNA的5'UTR，上调P3 mRNA及IGF-II蛋白表达，初步显示其调控机制不同于目前已证实的miRNA调控基因表达的方式。为此，本项目在前期工作基础上，进一步探讨5p上调P3 mRNA及IGF-II蛋白表达的可能机制，以及5p与HCC预后的关系。拟解决的关键科学问题是：5p是否在细胞核中与某些未知蛋白组成5p-蛋白复合物，进而与P3 mRNA结合上调其表达。本项目的实施将对5p调控基因表达机制的认识提高到一个新的高度，同时也为肝癌治疗、早期诊断和预后监测提供新思路和分子靶标。

Evidence has shown that miRNAs are implicated in a variety of biological processes, such as cell proliferation, apoptosis, tumorigenesis, etc by regulating gene expression via the mechanisms of transcriptional or posttranscriptional suppression or activation. It has been indicated that miR-483-5p, an intronic miRNA of the IGF-II gene, is associated with the development and prognosis of multiple human cancers, but the role of it in HCC is not clarified. We have showed that miR-483-5p upregulates P3 mRNA and IGF-II protein expression by targeting the 5′UTR of P3 mRNA in HCC cells, and the mechanism that contributes to this upregulation may differ from the confirmed ways by which miRNAs regulate gene expression. Our present study is to explore the mechanism responsible for the upregulation of P3 mRNA and IGF-II protein expression by miR-483-5p, and the relationship between miR-483-5p and the prognosis of HCC patients. The key scientific problem is that whether miR-483-5p can bind to unknown proteins in HCC cell nuclei, and then upregulates P3 mRNA and IGF-II protein expression by binding to P3 mRNA 5′UTR. The implementation of our study can not only improve understanding of regulation mechanism of gene expression mediated by miR-483-5p, but also provide new ideas and a molecular target for the treatment, early diagnosis, and prognostic monitoring of HCC.