RFX5 位于染色体1q21 ，编码具有转录激活功能的DNA结合蛋白。根据文献报道该区段在约57%的HCC 患者基因组中有扩增。我们前期研究发现RFX5 的编码基因在部分HCC 患者和多个HCC 细胞系中存在拷贝数扩增，在70%以上的HCC 患者和多个HCC 细胞系中过度表达。并且,部分过表达RFX5的HCC 细胞系，其增殖和克隆形成能力依赖于RFX5 ，提示RFX5在HCC的发生发展中具有重要的作用。ChIP-seq的 数据显示：RFX5 能够结合Cyclin D1 (CCND1)、MYC、CDK4、MDM2 和MDM4等细胞周期调控基因的转录调控区域，提示RFX5 可能参与细胞周期的调控，肝癌中过表达的RFX5 可能通过上调细胞周期相关基因的表达水平，致使细胞周期失调控，进而发展为原发性肝细胞癌。因此本研究拟在前期研究的基础上，深入研究RFX5 在HCC发生发展中的作用及其分子机制。

RFX5 is located at 1q21 and encoded a transactivating DNA binding regulatory factor, involved in MHC class II expression,binding the MHC promotor box X. 1q21 was reported to amplificated in about 57% of HCC patients acording to previous publications. In previous study, we found that the RFX5 coding region amplified in most HCC patients and HCC cell lines. The RFX5 mRNA and proteins also overexpressed in over 70% of HCC patients and HCC cell lines. Strikingly, the proliferation and clonoenic growth potential of these RFX5-amplified cell lines was significantly reduced by the silencing of RFX5 exprssion. Furthermore, ChIP-seq data of RFX5 showed that RFX5 can bind to the transcription regulatory region of cell cycle check point genes, such as Cyclin D1, MYC, CDK4, MDM2 and MDM4.These data suggest that RFX5 is a candidate HCC oncogene which involved in the HCC carcinogenesis process by transcriptionally activating pro-proliferation genes and lead to uncontroled proliferation of liver cells and tumor.Hence, this project aims to study the role of RFX5 in the carcinogenesis of HCC and it's molecular mechanism.

我们的研究证实RFX5编码基因在HCC组织和细胞系中扩增并且过度表达，并且其mRNA表达水平与HCC患者的术后无瘤生存时间相关。细胞生物学实验也发现部分HCC细胞系的克隆形成能力依赖于过度表达的RFX5基因。这些结果提示，RFX5可能在HCC的发生发展中具有重要的作用。进一步的研究发现，HCC细胞中的RFX5能够结合YWHAQ、KDM4A和TPP1基因的转录调控区域，而且在IFN-γ刺激下， HCC细胞中的RFX5还能进一步结合的MAPK3、NPLOC4和SON基因的转录调控区域。这些候选的下游靶基因，均是可以参与肿瘤发生发展的基因。其中，TPP1、YWHAQ、NPLOC4和SON的mRNA表达水平均和HCC患者的术后无瘤生存时间相关。因此，RFX5很可能通过对这些基因的转录调控，参与HCC的发生发展过程。