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

Figures

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  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.

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  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.

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  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.