Abstract
The intricate molecular network shared between diabetes mellitus (DM) and cancer has been broadly understood. DM has been associated with several hormone-dependent malignancies, including breast, pancreatic, and colorectal cancer (CRC). Insulin resistance, hyperglycemia, and inflammation are the main pathophysiological mechanisms linking DM to cancer. Non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are widely appreciated as pervasive regulators of gene expression, governing the evolution of metabolic disorders, including DM and cancer. The ways ncRNAs affect the development of DM complicated with cancer have only started to be revealed in recent years. Insulin-like growth factor 1 receptor (IGF-1R) signaling is a master regulator of pathophysiological processes directing DM and cancer. In this review, we briefly summarize a number of well-known miRNAs and lncRNAs that regulate the IGF-1R in DM and cancer, respectively, and further discuss the potential underlying molecular pathogenesis of this disease association.
Highlights
Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, which arises from insufficient insulin secretion, insulin resistance, or augmented glucagon production
It was found that long non-coding RNAs (lncRNAs) H19 inhibition is concomitant with Insulin-like growth factor 1 receptor (IGF-1R) up-regulation instead of down-regulation; this process is mediated by the miR-675 transcribed from H19 locus, suggesting that H19 regulation loops plays a pivotal role in determining the direction of regulation [115]
We discussed a number of well-known miRNAs and lncRNAs that regulate IGF-1R signaling in diabetes mellitus (DM) and cancer, and further highlight the potential underlying molecular pathogenesis of their comorbidity
Summary
Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, which arises from insufficient insulin secretion, insulin resistance, or augmented glucagon production. Considering obesity is a cause of the vast majority of T2DM diabetes, one underlying pathogenic mechanism could involve inflammation within adipose tissue with production of cytokines that interfere with insulin signaling, leading to resistance to insulin and decreased glucose clearing. The latter stimulates the pancreas to generate insulin, which leads to relative hyperinsulinemia [11,12]. The insulin receptor (IR) and the IGF-1R, prevalently dysregulated signaling pathways in cancer and DM, have been reported to regulate or be regulated at different levels by ncRNAs [13] This integrative loop finely tunes multiple biological processes. We aim to discuss the interaction between ncRNAs and the IGF-1R in the regulation of the carcinogenic process in patients with DM
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