Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in cancer

Xinwei Huang,Xiangyang Kong,Hong Zhang,Xiaoran Guo,Zongxin Zhu,Haibo Cai

doi:10.1186/s13045-018-0628-y

Abstract

The insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1) plays essential roles in embryogenesis and carcinogenesis. IGF2BP1 serves as a post-transcriptional fine-tuner regulating the expression of some essential mRNA targets required for the control of tumor cell proliferation and growth, invasion, and chemo-resistance, associating with a poor overall survival and metastasis in various types of human cancers. Therefore, IGF2BP1 has been traditionally regarded as an oncogene and potential therapeutic target for cancers. Nevertheless, a few studies have also demonstrated its tumor-suppressive role. However, the details about the contradictory functions of IGF2BP1 are unclear. The growing numbers of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been identified as its direct regulators, during tumor cell proliferation, growth, and invasion in multiple cancers. Thus, the mechanisms of post-transcriptional modulation of gene expression mediated by IGF2BP1, miRNAs, and lncRNAs in determining the fate of the development of tissues and organs, as well as tumorigenesis, need to be elucidated. In this review, we summarized the tissue distribution, expression, and roles of IGF2BP1 in embryogenesis and tumorigenesis, and focused on modulation of the interconnectivity between IGF2BP1 and its targeted mRNAs or non-coding RNAs (ncRNAs). The potential use of inhibitors of IGF2BP1 and its related pathways in cancer therapy was also discussed.

Highlights

The insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1), a member of a conserved family of single-stranded RNA-binding proteins (IGF2BP1-3), expresses in a broad range of fetal tissues and more than 16 cancers but only in a limited number of normal adult tissues
We provided a new overview of the roles of IGF2BP1 in embryo development and in multiple cancers
We focused on the interconnectivity between IGF2BP1 and its targeted mRNAs or non-coding RNAs (ncRNAs) involved in the biological processes of embryogenesis and tumorigenesis, as well as aid in the identification of potential targets for cancer therapy and contribute to the cancer drug-discovery research

Summary

Background

The insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1), a member of a conserved family of single-stranded RNA-binding proteins (IGF2BP1-3), expresses in a broad range of fetal tissues and more than 16 cancers but only in a limited number of normal adult tissues. In numerous studies in vivo and in vitro, the emerging cancer-related mRNAs have been found, including PTEN, ACTB, MAPK4, MKI67, c-MYC, and CD44 By regulating those mRNAs, IGF2BP1 has been identified to play important roles in cell proliferation and growth of normal tissues and tumor tissues, as well as tumor cell adhesion, apoptosis, migration, and invasion [8]. Some miRNAs including miR-506 and miR-873 were showed to be lowly expressed in GBM tissues or cells and play a tumor-suppressive role in this disease by targeting and modulating IGF2BP1 Their overexpression was observed to repress the cell proliferation and migration, and invasion of GBM through downregulating the IGF2BP1 levels, which reduces the level of c-MYC, CD44, MKI67, and PTEN mRNA in GBM cells or blocks G1/S transition in glioblastoma cell [44, 83]. The depletion of ribosomal protein S6 kinase (RSK2) or protein phosphatase methylesterase 1 (PPME1) inhibits cell migration and invasion, which is similar to that after knockdown of IGF2BP1 that controls RSK2 and PPME expression,

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