PCGF1-ZBTB16-糖酵解通路促进肺癌增殖和转移的机制研究

在肺癌发病率、死亡率双高的大背景下，阐明肺癌增殖和转移的分子机制是目前肺癌研究领域亟需解决的关键科学问题。泛素化修饰是蛋白质翻译后修饰的关键形式，E3连接酶在其中发挥着最关键的作用。PCGF1具有E3连接酶活性，其在肺癌中的作用及分子机制目前尚未报道。前期工作显示：PCGF1的表达与肺癌临床转移、分期及预后密切相关；PCGF1促进肺癌细胞的增殖及转移，参与调控肺癌细胞糖酵解；PCGF1蛋白与ZBTB16蛋白相互作用。本项目中我们将进一步阐明：①PCGF1-ZBTB16-糖酵解通路在肺癌增殖和转移中的作用；②PCGF1-ZBTB16-糖酵解通路的调控分子机制；③PCGF1-ZBTB16-糖酵解通路在肺癌中的临床意义。本项目的预期成果将首次揭示PCGF1促进肺癌增殖和转移的分子机制，为发现新的抗肺癌潜在药物靶点提供重要线索。本项目具有扎实的研究背景和基础，具有可行性、创新性和潜在的临床价值。

In the context of the high incidence and mortality of lung cancer, the elucidation of the underlying mechanism for lung cancer proliferation and metastasis is one of the key scientific issues that need to be addressed urgently in the field of lung cancer. Ubiquitination modification is one of the key forms of protein post-translational modification, in which E3 ligase plays the most critical role. PCGF1 possesses intrinsic E3 ligase activity.However,its biological functions and related molecular mechanism in lung cancer development and progression are largely unknown.In our preliminary experiments, we have demonstrated that the expression of PCGF1 is closely associated with metastasis,advanced tumor stages and poor survival;PCGF1 can promote the growth and metastasis of lung cancer cells and participate in the regulation of metabolic function ;PCGF1 protein interacts with ZBTB16 protein. Based on these previous results, we aim to answer the key scientific questions including that: 1)the role of PCGF1-ZBTB16-glycolysis pathway in the proliferation and metastasis of lung cancer;2)The regulatory molecular mechanism of PCGF1-ZBTB16-glycolysis pathway; 3) The clinical significance of PCGF1-ZBTB16-glycolysis pathway in lung cancer.This study is the first to explore the mechanism underlying the promote effect of PCGF1 on lung cancer cell growth through the regulation of cellular energetics，and provide important clues for discovering new potential drug targets to intervene the progression of lung cancer. Taken together，given the solid research background and preliminary data，we strongly believe that this study is definitely feasible，innovative and has the potentialclinical translation implications.