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Review
. 2021 Nov 14;22(22):12303.
doi: 10.3390/ijms222212303.

Tumor-Progressive Mechanisms Mediating miRNA-Protein Interaction

Hiroaki Konishi  1 , Hiroki Sato  2 , Kenji Takahashi  2 , Mikihiro Fujiya  1   2
Affiliations
Review

Tumor-Progressive Mechanisms Mediating miRNA-Protein Interaction

Hiroaki Konishi et al. Int J Mol Sci. .

Abstract

MicroRNAs (miRNAs) are single-stranded short-chain RNAs that are endogenously expressed in vertebrates; they are considered the fine-tuners of cellular protein expression that act by modifying mRNA translation. miRNAs control tissue development and differentiation, cell growth, and apoptosis in cancer and non-cancer cells. Aberrant regulation of miRNAs is involved in the pathogenesis of various diseases including cancer. Numerous investigations have shown that the changes in cellular miRNA expression in cancerous tissues and extracellular miRNAs enclosed in exosomes are correlated with cancer prognosis. Therefore, miRNAs can be used as cancer biomarkers and therapeutic targets for cancer in clinical applications. In the previous decade, miRNAs have been shown to regulate cellular functions by directly binding to proteins and mRNAs, thereby controlling cancer progression. This regulatory system implies that cancer-associated miRNAs can be applied as molecular-targeted therapy. This review discusses the roles of miRNA-protein systems in cancer progression and its future applications in cancer treatment.

Keywords: RNA-binding protein; cancer therapy; microRNA.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Working system of microRNA (miRNA) targeting RNA-binding protein (RBP). RBPs support the regulation of translation by binding to messenger RNAs (mRNAs) (A). Conversely, microRNA (miRNA)-containing RNA-induced silencing complexes (RISCs) suppress the translation through the sequence-dependent binding to mRNAs (B). Some miRNAs, which have similar sequences with RNA-binding domains of RBP, can be decoy mRNA and interfere with the translation mediating the RBP–mRNA binding (C) and induce RBP ubiquitination mediating the direct binding (D).
Figure 2
Figure 2
Decoy system mediating miRNA. miR-328 directly binds to the KH domain of hnRNP E2 and inhibits the binding of hnRNP E2 and CEBPA mRNA, thereby accelerating the translation of CEBPA mRNA (A). miR-26a and 584 directly bind to the RRM domain of hnRNP A1 and inhibit the binding of hnRNP A1 and CDK6 mRNA, thereby inducing the destabilization of CDK6 mRNA (B).
Figure 3
Figure 3
Methodology for the identification of RNA-binding protein (RBP)-binding micro RNAs (miRNAs) and messenger RNAs (mRNAs). RNA-IP with microarray analysis is a powerful strategy to exhaustively identify unknown PBP-miRNA or messenger RNA (mRNA) interactions. miRNAs and mRNAs, which interact with a specific RNA-binding protein (RBP) in cancer cells, are subjected to pulldown assays by immunoprecipitation using anti-RBP antibodies extracted through the phenol–chloroform extraction method and identified via microarray analysis.
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