MiRNA dysregulation underlying common pathways in type 2 diabetes and cancer development: an Italian Association of Medical Oncology (AIOM)/Italian Association of Medical Diabetologists (AMD)/Italian Society of Diabetology (SID)/Italian Society of Endocrinology (SIE)/Italian Society of Pharmacology (SIF) multidisciplinary critical view

Abstract

Increasing evidence suggests that patients with diabetes, particularly type 2 diabetes (T2D), are characterized by an increased risk of developing different types of cancer, so cancer could be proposed as a new T2D-related complication. On the other hand, cancer may also increase the risk of developing new-onset diabetes, mainly caused by anticancer therapies. Hyperinsulinemia, hyperglycemia, and chronic inflammation typical of T2D could represent possible mechanisms involved in cancer development in diabetic patients. MicroRNAs (miRNAs) are a subset of non-coding RNAs, ⁓22 nucleotides in length, which control the post-transcriptional regulation of gene expression through both translational repression and messenger RNA degradation. Of note, miRNAs have multiple target genes and alteration of their expression has been reported in multiple diseases, including T2D and cancer. Accordingly, specific miRNA-regulated pathways are involved in the pathogenesis of both conditions. In this review, a panel of experts from the Italian Association of Medical Oncology (AIOM), Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology (SIE), and Italian Society of Pharmacology (SIF) provide a critical view of the evidence about the involvement of miRNAs in the pathophysiology of both T2D and cancer, trying to identify the shared miRNA signature and pathways able to explain the strong correlation between the two conditions, as well as to envision new common pharmacological approaches.

Keywords: cancer; miRNA-based drugs; miRNAs; type 2 diabetes.

Figure 1

We identified the main microRNAs (miRNAs) involved in the pathophysiology of type 2 diabetes, for which a direct role has been shown in mediating pancreatic β-cell dysfunction and death and the onset of peripheral insulin resistance (green circles), the two hallmarks of type 2 diabetes pathogenesis. Among them, we have identified miRNAs also involved in cancer pathogenesis (miRNAs in bold in the pink boxes). We have then carried out target prediction and functional annotation using the miRSystem database, identifying 25 miRNAs (blue circle) that participate in pathways involved in both type 2 diabetes and cancer (olive green box). IRS, insulin receptor substrates; MAPK, mitogen-activated protein kinase; mTOR, mammalian target of rapamycin; PI3K, phosphatidylinositol 3-kinase.