文章：

胰岛素样生长因子II mRNA结合蛋白1通过监测CDC25A mRNA调控胰腺癌细胞生长

Insulin-like Growth Factor II mRNA-Binding Protein 1 Regulates Pancreatic Cancer Cell Growth through the Surveillance ofCDC25AmRNA

原文发布日期：13 October 2023

DOI: 10.3390/cancers15204983

类型: Article

开放获取: 是

英文摘要：

A number of data indicate that the sources of different kinds of PDAC may be discovered at the transcription/transduction stage. RNA metabolism is manipulated at various steps by different RNA-binding proteins (RBPs), and the deregulation or irregular activity of RBPs is known to contribute to tumor promotion and progression. The insulin-like growth factor 2 mRNA-binding protein family (IMPs), and IMP1 in particular, has been linked with a poor prognosis in PDAC patients; however, little is known about its contribution in PDAC carcinogenesis. In this study, we investigated the function of IMP1 in PDAC. To evaluate IMP1 expression and correlation with PDAC prognosis, we utilized several public databases. Using a specific siRNA IMP1, we analyzed cell death and cell cycle progression in PDAC cell lines and 3D spheroids. The role of IMP1 was also evaluated in vivo in a Panc-1-derived tumor xenograft murine model. Public data suggest that PDAC patients with higher expression of IMP1 showed poor overall and progression-free survival. IMP1 silencing leads to reduced cell growth in PDAC cells and three-dimensional spheroids. Abrogation of IMP1 in PDAC cells showed lower levels ofCDC25A, increased phosphorylation of the cyclin-dependent kinase (CDK)2, and accumulation of PDAC cells in the G1 phase. Immunoprecipitation experiments revealed that IMP1 bindsCDC25AmRNA, thus controlling cell-cycle progression. Ultimately, we proved that suppression of IMP1 blocked in vivo growth of Panc-1 transferred into immunodeficient mice. Our results indicate that IMP1 drives the PDCA cell cycle and represents a novel strategy for overcoming PDCA cell proliferation.

摘要翻译： 

多项数据表明，不同亚型胰腺导管腺癌（PDAC）的起源可能在转录/转导阶段被发现。RNA代谢在不同步骤中受到多种RNA结合蛋白（RBPs）的调控，而RBPs的失调或异常活性已知会促进肿瘤的发生与发展。胰岛素样生长因子2 mRNA结合蛋白家族（IMPs），特别是IMP1，已被证实与PDAC患者的不良预后相关；然而，其在PDAC癌变过程中的具体作用尚不明确。本研究旨在探讨IMP1在PDAC中的功能。为评估IMP1表达及其与PDAC预后的相关性，我们利用多个公共数据库进行分析。通过特异性siRNA沉默IMP1，我们在PDAC细胞系和三维球状培养模型中分析了细胞死亡和细胞周期进程。同时，在Panc-1来源的肿瘤异种移植小鼠模型中评估了IMP1的体内作用。公共数据显示，IMP1高表达的PDAC患者总体生存期和无进展生存期均较差。沉默IMP1可抑制PDAC细胞及三维球状体的生长。在PDAC细胞中敲低IMP1导致CDC25A水平降低、细胞周期蛋白依赖性激酶（CDK）2磷酸化增强，并使细胞停滞于G1期。免疫共沉淀实验证实IMP1直接结合CDC25A mRNA，从而调控细胞周期进程。最终，我们证明抑制IMP1能够阻断移植至免疫缺陷小鼠体内的Panc-1肿瘤生长。本研究结果表明，IMP1驱动PDAC细胞周期进程，这为抑制PDAC细胞增殖提供了新的潜在治疗策略。

原文链接：

Insulin-like Growth Factor II mRNA-Binding Protein 1 Regulates Pancreatic Cancer Cell Growth through the Surveillance ofCDC25AmRNA