Shaanxi Eye Hospital (Xi'an People's Hospital), Affiliated Guangren Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an 71004, Shaanxi Province, China.
Division of Experimental Neurosurgery, Department of Neurosurgery, University of Heidelberg, Heidelberg 69120, Germany.
J Clin Endocrinol Metab. 2021 Sep 27;106(10):2807-2818. doi: 10.1210/clinem/dgab391.
Type 2 diabetes mellitus (T2DM) and cancer share a variety of risk factors and pathophysiological features. It is becoming increasingly accepted that the 2 diseases are related, and that T2DM increases the risk of certain malignancies.
This review summarizes recent advancements in the elucidation of functions of insulin-like growth factor 2 (IGF-2) messenger RNA (mRNA)-binding protein 2 (IGF2BP2) in T2DM and cancer.
A PubMed review of the literature was conducted, and search terms included IGF2BP2, IMP2, or p62 in combination with cancer or T2DM. Additional sources were identified through manual searches of reference lists. The increased risk of multiple malignancies and cancer-associated mortality in patients with T2DM is believed to be driven by insulin resistance, hyperinsulinemia, hyperglycemia, chronic inflammation, and dysregulation of adipokines and sex hormones. Furthermore, IGF-2 is oncogenic, and its loss-of-function splice variant is protective against T2DM, which highlights the pivotal role of this growth factor in the pathogenesis of these 2 diseases. IGF-2 mRNA-binding proteins, particularly IGF2BP2, are also involved in T2DM and cancer, and single-nucleotide variations (formerly single-nucleotide polymorphisms) of IGF2BP2 are associated with both diseases. Deletion of the IGF2BP2 gene in mice improves their glucose tolerance and insulin sensitivity, and mice with transgenic p62, a splice variant of IGF2BP2, are prone to diet-induced fatty liver disease and hepatocellular carcinoma, suggesting the biological significance of IGF2BP2 in T2DM and cancer.
Accumulating evidence has revealed that IGF2BP2 mediates the pathogenesis of T2DM and cancer by regulating glucose metabolism, insulin sensitivity, and tumorigenesis. This review provides insight into the potential involvement of this RNA binding protein in the link between T2DM and cancer.
2 型糖尿病（T2DM）和癌症具有多种共同的风险因素和病理生理特征。越来越多的人认为这两种疾病是相关的，T2DM 会增加某些恶性肿瘤的风险。
本综述总结了胰岛素样生长因子 2（IGF-2）mRNA 结合蛋白 2（IGF2BP2）在 T2DM 和癌症中功能的最新研究进展。
通过 PubMed 文献检索，检索词包括 IGF2BP2、IMP2 或 p62 与癌症或 T2DM 相结合。通过手动检索参考文献，进一步确定了其他来源。人们认为，T2DM 患者发生多种恶性肿瘤和与癌症相关的死亡的风险增加，原因是胰岛素抵抗、高胰岛素血症、高血糖、慢性炎症以及脂联素和性激素失调。此外，IGF-2 具有致癌性，其功能丧失的剪接变体可预防 T2DM，这突出表明该生长因子在这两种疾病的发病机制中起着关键作用。IGF-2 mRNA 结合蛋白，特别是 IGF2BP2，也与 T2DM 和癌症有关，IGF2BP2 的单核苷酸变异（以前称为单核苷酸多态性）与这两种疾病都有关。在小鼠中删除 IGF2BP2 基因可改善其葡萄糖耐量和胰岛素敏感性，而具有转基因 p62（IGF2BP2 的剪接变体）的小鼠易患饮食诱导的脂肪肝和肝细胞癌，这表明 IGF2BP2 在 T2DM 和癌症中的生物学意义。
越来越多的证据表明，IGF2BP2 通过调节葡萄糖代谢、胰岛素敏感性和肿瘤发生来介导 T2DM 和癌症的发病机制。本综述深入了解了这种 RNA 结合蛋白在 T2DM 和癌症之间关联中的潜在作用。
