Nucleolin promotes tumor growth in colorectal cancer by enhancing hnRNPA1-mediated PKM2 alternative splicing  

作　　者：Xue Wang Han Cheng Die Hu Ying Chen Waseem Hassan Jing Zhao Jiuming Li Zhaohui Huang 

机构地区：[1]Laboratory of Cancer Epigenetics,Wuxi School of Medicine,Jiangnan University,Wuxi,Jiangsu 214062,China [2]Wuxi Cancer Institute,Affiliated Hospital of Jiangnan University,Wuxi,Jiangsu 214062,China [3]Wuxi School of Medicine,Jiangnan University,Wuxi,Jiangsu 214062,China [4]Department of Pharmacy,COMSATS University Islamabad,Lahore Campus,Lahore 54000,Pakistan

出　　处：《Genes & Diseases》2023年第6期2237-2240,共4页基因与疾病（英文）

基　　金：supported by the National Natural Science Foundation of China(No.81802462,81972220,and 82173063);the Natural Science Foundation of Jiangsu Province,China(No.BK20180618 and BE2019632);Wuxi Taihu Lake Talent Plan,and Wuxi Medical Key Discipline(China)(No.ZDXK2021002);China Postdoctoral Science Foundation(No.2020M681493);Postdoctoral Science Foundation of Jiangsu Province,China(No.2020Z050);Fundamental Research Funds for the Central Universities(China)(No.JUSRP11952).

摘　　要：Emerging evidence indicates that metabolism reprogramming plays an important role in cancer progression.RNAbinding protein nucleolin(NCL)was reported to function as an important oncogenic factor in multiple cancer types.However,the role and mechanism of NCL in cancer metabolism are unknown.In this study,we found that NCL directly interacted with hnRNPA1 and promoted CRC cell proliferation by enhancing aerobic glycolysis.Mechanistically,NCL bound PKM pre-mRNA and increased hnRNPA1-mediated PKM alternative splicing,resulting in increased PKM2 expression and tumor growth.A seed-mediated growth approach was used to synthesize gold nanostars(GNS),which were further modified with aptamer AS1411(an NCL ligand),GE11(an EGFR ligand),and nuclear localization signal to obtain functionalized nanoparticles(GNSAS1411-GE11).GNS-AS1411-GE11 efficiently enter the nucleus of CRC cells and blocked the glycolysis-promoting effects of NCL,inhibiting the growth of CRC xenograft.Targeting NCL is a promising strategy for treating CRC.

关 键 词：PKM2 METABOLISM MEDIATED 

分 类 号：R73[医药卫生—肿瘤]