Insulin-like growth factor 2 mRNA binding protein 2 promotes aerobic glycolysis and cell proliferation in pancreatic ductal adenocarcinoma via stabilizing GLUT1 mRNA
Insulin-like growth factor 2 mRNA binding protein 2 promotes aerobic glycolysis and cell proliferation in pancreatic ductal adenocarcinoma via stabilizing GLUT1 mRNA
复制标题
胰岛素样生长因子 2 mRNA 结合蛋白 2 通过稳定 GLUT1 mRNA 促进胰腺导管腺癌中的有氧糖酵解和细胞增殖
DOI：
10.1093/abbs/gmz048
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发表时间：
2019-07-01
影响因子：
3.7
通讯作者：
Hao, Linlin
中科院分区：
文献类型：
--
作者：
Huang, Shan;Wu, Zheng;Hao, Linlin
胰岛素样生长因子2 mRNA结合蛋白2（IGF2BP2）是IGF2BP蛋白家族的成员，由IGF2BP1类似于3组成，具有结合多种转录物并调节RNA稳定性、定位和翻译的能力。在这项研究中，我们发现IGF2BP2的表达上调，导致胰腺导管腺癌（PDAC）的预后不良。在LSL-Kras（G12 D/+）; LSL-Trp53（R172 H/+）; Pdx 1-Cre小鼠模型中，IGF2BP2蛋白从正常胰腺、胰腺上皮内瘤变到PDAC逐渐升高。此外，我们证明IGF2BP2通过直接结合和稳定GLUT1 mRNA促进有氧糖酵解和PDAC细胞增殖。总之，我们的研究揭示了IGF2BP2通过调节有氧糖酵解在PDAC发展中的重要作用，并作为PDAC治疗的潜在治疗靶点。
Insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) is a member of the IGF2BP protein family consisting of IGF2BP1 similar to 3 with the capacity of binding to many transcripts and regulating RNA stability, localization, and translation. In this study, we discovered that expression of IGF2BP2 was upregulated and led to a poor prognosis in pancreatic ductal adenocarcinoma (PDAC). IGF2BP2 protein was gradually elevated from normal pancreas, pancreatic intraepithelial neoplasia to PDAC in an LSL-Kras(G12D/+);LSL-Trp53(R172H/+);Pdx1-Cre mouse model. Furthermore, we demonstrated that IGF2BP2 promoted aerobic glycolysis and PDAC cell proliferation through directly binding to and stabilizing GLUT1 mRNA. In summary, our study unveiled an important role of IGF2BP2 in PDAC development by modulating aerobic glycolysis and as a potential therapeutic target for PDAC treatment.