Non-Coding RNAs in IGF-1R Signaling Regulation: The Underlying Pathophysiological Link between Diabetes and Cancer

Baoqing Chen, Junyan Li, Dongmei Chi, Iman Sahnoune, Steliana Calin, Leonard Girnita, George A Calin, Baoqing Chen, Junyan Li, Dongmei Chi, Iman Sahnoune, Steliana Calin, Leonard Girnita, George A Calin

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.

Keywords: IGF-1R; cancer; diabetes; lncRNAs; micoRNAs.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Insulin-like growth factor (IGF)-insulin receptor (IR) signaling and the regulating of insulin-like growth factor 1 receptor (IGF-1R) by long non-coding RNAs (lncRNA). The activation of IGF-1R, IR or hybrid IR/IGF-1R leads to the activation of two main downstream pathways: 1) RAS-RAF-MAPK/ERK; 2) PI3K-AKT-mTOR, to regulate metabolic processes and tumor growth; the lncRNA inhibits the IGF-1R either directly, or by acting as a sponge for the microRNAs (miRNA) interactors with IGF-1R, or as a platform connecting the interaction molecularly. Non-coding RNAs (ncRNAs) that regulate non-kinase signaling or are regulated by IGF-1R warrant further investigation.
Figure 2
Figure 2
The synthesis and biological function of miRNAs and lncRNAs. A. Precursor miRNA (pre-miRNA) is transported from the nucleus to the cytoplasm and cleaved by Dicer to produce the miRNA duplex. One strand of the duplex would be assembled into the miRNA-induced silencing complex (RISC) with the Argonaute protein and other co-factors. By base-pairings between miRNAs and their complementary sequences in the 3’-untranslated region (3′-UTR) of target mRNA, RISCs binds to the target mRNAs and suppresses its translation or induces its degradation to regulate the down-stream biological process. B. lncRNA regulates the biological processes of cells through four main mechanisms as described in the main text.
Figure 3
Figure 3
MiRNAs regulate the IGF-1R in diabetes mellitus (DM) and cancer. Green boxes highlight the suppressing role of miRNAs on the growth of specified types of cancer, inhibiting the progression of tumorigenesis. Red boxes represent the promoting effect of miRNAs on the growth of the specified kind of cancer.

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Source: PubMed

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