Biegel Jason M, Dhamdhere Mayura, Gao Shuang, Gowda Chethana P, Kawasawa Yuka Imamura, Spiegelman Vladimir S
Division of Hematology and Oncology, Pediatric Department, Penn State College of Medicine, Hershey, PA, United States.
Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, United States.
Front Oncol. 2021 Mar 16;11:608816. doi: 10.3389/fonc.2021.608816. eCollection 2021.
Gain at chromosome 17q21 in neuroblastoma is associated with a poor prognosis, independent of MYCN amplification status. Several potential proto-oncogenes have been identified in this region, one of them-insulin-like growth-factor-2 mRNA binding protein (IGF2BP1)-is expressed at high levels in stage 4 tumors, and associated with overall lower patient survival. Here, we demonstrate that down-regulation of IGF2BP1 activity, either by transcript silencing or chemical inhibition, suppresses neuroblastoma cell growth. Furthermore, the combination of IGF2BP1 inhibition along with commonly used chemotherapeutics that broadly affect DNA synthesis, or cyclin-dependent kinase (CDK) inhibitors that disrupt signal transduction, have a synergistic effect on the suppression of neuroblastoma cell proliferation.
神经母细胞瘤中17q21染色体的扩增与预后不良相关，与MYCN扩增状态无关。该区域已鉴定出几种潜在的原癌基因，其中之一——胰岛素样生长因子2 mRNA结合蛋白（IGF2BP1）——在4期肿瘤中高表达，并与患者总体生存率较低相关。在此，我们证明，通过转录沉默或化学抑制下调IGF2BP1活性可抑制神经母细胞瘤细胞生长。此外，IGF2BP1抑制与广泛影响DNA合成的常用化疗药物或破坏信号转导的细胞周期蛋白依赖性激酶（CDK）抑制剂联合使用，对抑制神经母细胞瘤细胞增殖具有协同作用。
