Therapeutic microRNA strategies in human cancer

Therapeutic microRNA strategies in human cancer - PubMed

Review

Therapeutic microRNA strategies in human cancer

Chunsheng Li et al. AAPS J. 2009 Dec.

Abstract

MicroRNAs (miRNAs) are approximately 22 nucleotide long, noncoding, endogenous RNA molecules which exert their functions by base pairing with messenger RNAs (mRNAs), thereby regulate protein-coding gene expression. In eukaryotic cells, miRNAs play important roles in regulating biological processes such as proliferation, differentiation, apoptosis, and stem cell self-renewal. The human genome may contain as many as 1,000 miRNAs, and more than 700 of them have been identified. miRNAs are predicted to target up to one third of mRNAs. Each miRNA can target hundreds of transcripts directly or indirectly, while more than one miRNA can converge on a single transcript target. Therefore, the potential regulatory circuitry afforded by miRNA is enormous. Recently, mounting evidence implicates miRNAs as a new class of modulator for human tumor initiation and progression. Therefore, it has been proposed that manipulating miRNA activity and miRNA biogenesis may be a novel avenue for developing efficient therapies against cancer.

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Figures

**Fig. 1**
Schematic diagram of miRNA biogenesis and the therapeutic strategies. 1 Anti-miRNA oligonucleotides (*AMO*) base pair with miRNA, therefore inhibit miRNA binding to target mRNAs; 2 mRNA sponges contain multiple binding sites for a specific miRNA which in turn prevent the binding of this miRNA with its endogenous targets; 3 miRNA mask DNA is complementary to miRNA binding site, resulting in gene-specific interference of miRNA:mRNA interaction; 4 small molecule inhibitor for *mir-21* has been reported to inhibit the level of mature miRNA as well as pri-miRNA; 5, 6 gene therapy using virus delivery system and nanoparticle can force the expression of specific tumor suppressive miRNA to achieve therapeutic effect; 7 targeting miRNA biogenesis has been proposed, however, the feasibility of this approach need future evaluation

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