结直肠癌是严重威胁人类健康的恶性肿瘤，其发病率和死亡率均位列全球第三位，至今其发病机制尚未充分了解。RNA结合蛋白核仁素(Nucleolin)在结直肠癌中发挥着癌基因的作用，但具体的分子机制尚不清楚。我们前期发现Nucleolin可与核不均一核糖核蛋白A1(hnRNPA1)结合，PKM2 mRNA是影响其结合的关键因素，并且hnRNPA1可促进细胞核中PKM2的可变剪切。据此我们假设，Nucleolin可能通过与hnRNPA1结合，影响其对PKM2 mRNA的可变剪切，并能进一步携带PKM2 mRNA由胞核向胞浆转位，从而增加胞浆中PKM2蛋白水平，进而调控肿瘤细胞糖代谢，促进肿瘤的发生发展。本研究拟通过分子实验及临床标本验证揭示Nucleolin通过hnRNPA1-PKM2通路调控结直肠癌糖代谢的新机制，为结直肠癌的防治提供新的思路。

Colorectal cancer (CRC) is a serious threat to human health and the 3rd leading cause of cancer-related incidences and mortalities. Though there is available data on CRC，the detailed mechanisms of CRC remains unclear. Previous data suggested that RNA binding protein Nucleolin plays oncogenic roles in CRC, but numerous details are missing in this link. By conducting systematic experiments, we discovered a Nucleolin interactor, hnRNPA1, that directly binds to Nucleolin under PKM2 mRNA conditions. The PKM2 alternative splicing occurred in the nucleus and was regulated by hnRNPA1. Based on these new findings, we hypothesis that Nucleolin enhances hnRNPA1-mediated PKM2 alternative splicing and then transports PKM2 mRNA from nucleus into cytoplasm by binding with hnRNPA1, resulting the increases of PKM2 protein expression in cytoplasm that promotes glucose metabolism and tumor development. The present study will try to reveal a novel pathway of Nucleolin-hnRNPA-PKM2 and its effects on glucose metabolism and tumor development in CRC by using the molecular assays as well as clinical samples analysis. This study reveals the new mechanism of Nucleolin regulated hnRNPA1-PKM2 pathway in the glucose metabolism that may serve as a prognostic biomarker and/or an effective target for CRC therapies.