Abstract
RNA network control is a key aspect of proper cellular homeostasis. In this context, RNA-binding proteins (RBPs) play a major role as regulators of the RNA life cycle due to their capability to bind to RNA sequences and precisely direct nuclear export, translation/degradation rates, and the intracellular localization of their target transcripts. Alterations in RBP expression or functions result in aberrant RNA translation and may drive the emergence and progression of several pathological conditions, including cancer. Among the RBPs, insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) is of particular interest in tumorigenesis and tumor progression. This review highlights the molecular mechanisms underlying the oncogenic functions of IGF2BP3, summarizes the therapeutic potential related to its inhibition and notes the fundamental issues that remain unanswered. To fully exploit IGF2BP3 for tumor diagnosis and therapy, it is crucial to dissect the mechanisms governing IGF2BP3 re-expression and to elucidate the complex interactions between IGF2BP3 and its target mRNAs as normal cells become tumor cells.
Highlights
RNA-binding proteins (RBPs), along with microRNAs and long noncoding RNAs, dictate the entire RNA life cycle from alternative splicing to nuclear export, transcript storage, stabilization, subcellular localization and degradation, representing major cotranscriptional and/or posttranscriptional regulators of gene expression
This review focuses on insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and its role in human cancer, highlighting the contradictions and discrepancies related to its still poorly understood mechanisms of action and the potential of this protein as diagnostic, prognostic and therapeutic biomarker
Important advancements have been achieved over the last years concerning our understanding of the oncogenic processes driven by RBPs, revealing that the relevance of these regulators in tumorigenesis and cancer progression has been largely underscored
Summary
RNA-binding proteins (RBPs), along with microRNAs (miRNAs; Box 1) and long noncoding RNAs (lncRNAs; Box 1), dictate the entire RNA life cycle from alternative splicing to nuclear export, transcript storage, stabilization, subcellular localization and degradation (for a review, please consider Coppin et al, 2018), representing major cotranscriptional and/or posttranscriptional regulators of gene expression. Chromatin immunoprecipitation (ChIP) assays (Box 1) confirmed the direct binding of the transcription factors Nanog and NF-κB to the IGF2BP3 promoter, sustaining its expression in tumor cells and favoring the stemness and migration properties, respectively (Chen et al, 2013; Bhargava et al, 2017).
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