Paip1及其介导的糖代谢重编程在乳腺癌增殖和周期进程中的作用机制研究

代谢重编程是肿瘤十大特征之一。研究显示，糖代谢重编程在肿瘤的恶性进展中发挥着重要作用。但有关糖代谢重编程在乳腺癌演进中的作用机制尚不明确。Paip1是真核生物翻译调控因子，其异常表达与肿瘤的发生发展密切相关。在前期研究中，我们发现Paip1蛋白在乳腺癌组织中显著高表达，并调控细胞增殖和周期进程；基因芯片分析发现差异表达基因富集于糖酵解通路，其中包括HK2、PKM2、LDHB、PGM1等糖酵解相关基因，说明Paip1蛋白与乳腺癌细胞糖酵解有重要的关联。综上，我们推测Paip1蛋白通过介导糖代谢重编程，调控乳腺癌细胞的增殖和周期进程。因此，本项目拟应用RNP-IP、氧消耗速率测定、Biotin-pull down等技术，探究Paip1及其介导的糖代谢重编程在乳腺癌演进中的作用及分子机制，并结合大样本的统计分析，为乳腺癌预后评估和治疗提供新分子标志物和靶点。

Metabolic reprogramming is considered as one of the 10 hallmarks of cancer. As well known, glucose metabolic reprogramming plays important role in carcinogenesis. However, the mechanism underlying glucose metabolic reprogramming in malignant transformation of breast cancer has not been fully elucidated. Paip1, as a translation regulator, participates in several cellular functions. In our previous study, we found that Paip1 was frequently overexpressed in breast cancer tissues, and could regulate cell proliferation and cell cycle process. In addition, the results of gene microarray revealed that the DEGs (Differentially expressed genes) were enriched in glycolysis, including HK2, PKM2, LDHB, PGM1 etc. These results suggest that Paip1 may involved in breast cancer glycolysis. Taken together, we hypothesis that Paip1 modulates breast cancer cell proliferation and cell cycle process through regulating glycolysis. Therefore, this study is aimed to use RNP-IP, oxygen consumption rate analysis, Biotin-pull down to explore the mechanisms of Paip1 in glycolysis in breast cancer. Then, bioinformatics analysis of large sample clinical cases will be utilized in hoping to provide novel target for therapeutic methods and prognosis evaluation.