hnRNP K是存在于细胞核中的重要转录调节蛋白，它通过与癌基因c-myc启动子区域的特定序列结合，上调c-myc的转录和表达并引发下游系列的分子事件。我们通过生物信息学和大量的体内外实验发现,表达该蛋白的基因hnRNP K启动子区域存在富G-序列，这些序列在形成稳定的G-四链体后，能够显著下调hnRNP K的转录和表达水平。本项目将在此重要发现基础上，结合本研究团队在G-四链体基因组研究中积累的经验和建立的技术平台，深入研究hnRNP K基因启动子G-四链体对该基因的转录和表达调控机制；进一步探讨hnRNP K蛋白通过c-myc基因启动子特殊核酸结构调控c-myc转录和表达的作用机制；设计和合成hnRNP K启动子G-四链体特异性的配体和探针，为上述分子机制研究提供有力的工具。本项目的研究，将为阐明重要癌基因c-myc的转录调控网络和通路，也为新型靶向性抗癌药物的研究提供新的理论依据。

hnRNP K is an important protein with transcriptional regulation function present in the nucleus, which increases the transcription and expression of c-myc causing subsequent downstream molecular effect, through its binding with special sequence on c-myc gene promoter region. In our recent bioinformatic and many in vivo and in vitro studies, we found several G-rich sequences on the upstream promoter of hnRNP K gene, could form G-quadruplexes in vitro, and down-regulate transcription and overexpression level of hnRNP K. Based on this important finding, in combination with our accumulated experience and technology platform in c-myc research, we plan to carry out in-depth mechanistic studies for transcriptional regulation of hnRNP K gene by these G-quadruplexes. We also plan to study the mechanism for hnRNP K protein to regulate c-myc gene transcription through its binding with c-myc promoter region. We will also design and synthesize highly selective binding ligands for hnRNP K promoter G-quadruplex as probes, providing powerful tools for the above mechanistic studies. This project will provide a new theoretical basis for elucidating transcriptional regulatory network and pathways of the important oncogene c-myc and discovery of anti-cancer drugs for new targets.