Non-small cell lung cancer (NSCLC) accompanied by diabetes is an important risk factor affecting the prognosis of patients with NSCLC in clinical practice. However, the effect of high glucose (HG) in the pathogenesis of NSCLC remains elusive. It has been found that the RNA-binding protein Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) plays important roles in various diseases, including NSCLC and diabetes. The aim of this study was to explore the role of IGF2BP1 in HG-treated NSCLC cells, and further investigate its underlying molecular mechanism. Results showed that IGF2BP1 was highly expressed in HG-treated NSCLC cells. Knockdown of IGF2BP1 inhibited cancer cell proliferation, migration and invasion, as well as induced cell cycle arrest and apoptosis. Besides, IGF2BP1 silencing decreased the Netrin-1 level in HG-treated NSCLC cells. Reintroduction of Netrin-1 expression rescued IGF2BP1 deficiency-induced cell proliferation reduction, migration suppression, cell cycle arrest and apoptosis. These findings suggest that IGF2BP1 silencing inhibits the occurrence of tumor events through down-regulating Netrin-1 expression, indicating that the IGF2BP1/Netrin-1 axis exerts an oncogenic role in HG-treated NSCLC cells.

在临床实践中，伴有糖尿病的非小细胞肺癌（NSCLC）是影响NSCLC患者预后的重要危险因素。但是，高糖（HG）在非小细胞肺癌的发病机理中的作用仍然难以捉摸。已经发现RNA结合蛋白胰岛素样生长因子2mRNA结合蛋白1（IGF2BP1）在包括NSCLC和糖尿病在内的多种疾病中起重要作用。这项研究的目的是探讨IGF2BP1在HG处理的NSCLC细胞中的作用，并进一步研究其潜在的分子机制。结果表明，IGF2BP1在经HG处理的NSCLC细胞中高表达。抑制IGF2BP1抑制癌细胞的增殖，迁移和侵袭，并诱导细胞周期停滞和凋亡。除了，IGF2BP1沉默降低了HG处理的NSCLC细胞的Netrin-1水平。重新引入Netrin-1表达可挽救IGF2BP1缺乏症诱导的细胞增殖减少，迁移抑制，细胞周期停滞和凋亡。这些发现表明，IGF2BP1沉默通过下调Netrin-1表达来抑制肿瘤事件的发生，表明IGF2BP1 / Netrin-1轴在经HG处理的NSCLC细胞中发挥致癌作用。