Insulin-like Growth Factor 2 mRNA-Binding Protein 2—a Potential Link Between Type 2 Diabetes Mellitus and Cancer

Abstract

Context Type 2 diabetes mellitus (T2DM) and cancer share a variety of risk factors and pathophysiological features. It is becoming increasingly accepted that the two 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) mRNA-binding protein 2 (IGF2BP2) in T2DM and cancer. Evidence Acquisition 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. Evidence Synthesis 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 two diseases. IGF-2 mRNA-binding proteins, particularly IGF2BP2, are also involved in T2DM and cancer, and 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. Conclusions Accumulating evidence 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.

Thyroid nodules of indeterminate cytology in Hispanic/Latinx patients

“…3 Type 2 DM is associated with greater risk for a variety of cancers, but there are conflicting data regarding the influence of T2DM, on DTC. [23][24][25] We found the highest number of malignant TN in patients with DM and elevated A1c (≥7%, 7/25 = 30.4%; p = 0.046), supporting an association between DTC and DM. However, given the small size of our cohort, this observation needs to be verified by larger, independent studies.…”

N6-methyladenosine (m6A) reader IGF2BP2 promotes gastric cancer progression via targeting SIRT1

“…In other cancers, IGF2BP2 has been reported to regulate numerous tumorigenesis [ 16–18 ]. For example, in hepatocellular carcinoma, researchers found that IGF2BP2 targets thousands of mRNA transcripts, which may be involved in the progression.…”

Advances in the study of RNA-binding proteins in diabetic complications

“…Another clinical trial suggested that the wild C allele of IGF2BP2 had a protective effect against T2DM in obese subjects of Chinese Han population [ 158 ]. IGF2BP2 can inhibit the expression of UCP1 by binding to UCP1 mRNA, thereby enhancing insulin resistant [ 159 , 160 ]. Furthermore, mTOR phosphorylates IGF2BP2 and facilitates its binding to IGF-2 mRNA, thus enhancing IGF-2 expression [ 160 , 161 ].…”

“…IGF2BP2 can inhibit the expression of UCP1 by binding to UCP1 mRNA, thereby enhancing insulin resistant [ 159 , 160 ]. Furthermore, mTOR phosphorylates IGF2BP2 and facilitates its binding to IGF-2 mRNA, thus enhancing IGF-2 expression [ 160 , 161 ].…”