microRNA-based diagnostic and therapeutic applications in cancer medicine - PubMed (original) (raw)

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microRNA-based diagnostic and therapeutic applications in cancer medicine

Lorenzo F Sempere et al. Wiley Interdiscip Rev RNA. 2021 Nov.

Abstract

It has been almost two decades since the first link between microRNAs and cancer was established. In the ensuing years, this abundant class of short noncoding regulatory RNAs has been studied in virtually all cancer types. This tremendously large body of research has generated innovative technological advances for detection of microRNAs in tissue and bodily fluids, identified the diagnostic, prognostic, and/or predictive value of individual microRNAs or microRNA signatures as potential biomarkers for patient management, shed light on regulatory mechanisms of RNA-RNA interactions that modulate gene expression, uncovered cell-autonomous and cell-to-cell communication roles of specific microRNAs, and developed a battery of viral and nonviral delivery approaches for therapeutic intervention. Despite these intense and prolific research efforts in preclinical and clinical settings, there are a limited number of microRNA-based applications that have been incorporated into clinical practice. We review recent literature and ongoing clinical trials that highlight most promising approaches and standing challenges to translate these findings into viable microRNA-based clinical tools for cancer medicine. This article is categorized under: RNA in Disease and Development > RNA in Disease.

Keywords: cancer; clinical trials; diagnostics; miR; miRNA; microRNA; noncoding RNA; therapeutic; tumor.

© 2021 The Authors. WIREs RNA published by Wiley Periodicals LLC.

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Conflict of interest statement

The authors have declared no conflicts of interest for this article.

Figures

FIGURE 1

FIGURE 1

Biological source and detection technologies for miRNA expression analysis. Sensitive and specific detection technologies enable detection of miRNAs from tumor tissue or bodily fluids. These biological samples can be used as bulk input for miRNA analysis or can be further processed with different methodologies to refine the cellular (e.g., cancer cells vs. immune cells in tissue samples) or circulating source (e.g., extracellular vesicles vs. cell‐free in plasma samples) of miRNAs. Key steps of detection and/or readout of each detection technology are shown (see Tables 1 and 2 for more details on studies applying these technologies). Molecules and constructs not drawn to scale. EVs, extracellular vesicles; FACS, fluorescence‐activated cell sorting; F or R primer, forward or reserve primer; PBMCs, peripheral blood mononuclear cells

FIGURE 2

FIGURE 2

Chemical modifications and delivery technologies. (a) Chemical structure of most common RNA analogue modifications incorporated in antisense miRNA inhibitor or double‐stranded mimics. (b) Representative examples of different chemical modification and delivery technologies (see Tables 4 and 5 for more details). Pattern and location of chemical modifications are representative of that particular approach and are approximation (in some cases the exact modified sequence is not fully disclosed). For miRNA mimics, top strand depicts the guide strand (mature miRNA) and bottom strand the passenger strand. Molecules and constructs not drawn to scale. 2′‐F, 2′‐Fluoro; 2′‐_O_‐me, 2′‐_O_‐methyl; 2′‐_O_‐MOE, 2′‐_O_‐methoxyethyl; Arg, arginine; LNA, locked nucleic acid; PEG, polyethylene glycol; PLGA, poly(lactic‐co‐glycolic acid); PNA, peptide nucleic acid; PO, phosphodiester; PS, phosphorothioate

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