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Human MicroRNA Targetome Indicates a Specialized Role of MicroRNAs in Regulation of Oncogenesis

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Systems Biology in Cancer Research and Drug Discovery

Abstract

MicroRNAs (miRNAs), a class of endogenous small noncoding RNAs, mediate posttranscriptional regulation of protein-coding genes by binding to the 3′ untranslated region of target mRNAs, leading to translational inhibition, mRNA destabilization or degradation. A single miRNA concurrently down-regulates hundreds of target mRNAs, and thereby fine-tunes gene expression involved in diverse cellular functions, such as development, differentiation, proliferation, apoptosis and metabolism. However, it remains unknown whether the set of miRNA target genes designated “targetome” regulated by an individual miRNA constitutes the biological network of functionally-associated molecules or reflects a random set of functionally-independent genes. To address this question, we studied the molecular network of the whole human miRNA targetome. Among 1,223 human miRNAs derived from miRbase Release 16, Diana-microT 3.0, a target prediction program, predicted reliable targets from 273 miRNAs. Among them, KeyMolnet, a bioinformatics tool for analyzing molecular interactions on the comprehensive knowledgebase, successfully extracted molecular networks from 232 miRNAs. In miRNA targetome networks, the most relevant pathway was transcriptional regulation by RB/E2F, important regulators of oncogenic transformation, the disease was adult T cell lymphoma/leukemia, and the pathological event was cancer, indicating that the human miRNA system termed “miRNAome” plays a specialized role in regulation of oncogenesis. The predicted targets derived from approximately 20 % of all human miRNAs construct biologically meaningful molecular networks, supporting the view that the miRNA targetome generally constitutes the biological network of functionally-associated molecules in human cells.

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Abbreviations

EMT:

Epithelial-mesenchymal transition

HPRD:

Human protein reference database

IPA:

Ingenuity pathways analysis

KEGG:

Kyoto encyclopedia of genes and genomes

miTG:

MicroRNA-targeted gene

MRE:

MicroRNA recognition elements

PPI:

Protein-protein interaction

RISC:

RNA-induced silencing complex

3′ UTR:

3′ Untranslated region

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Acknowledgements

The author thanks Dr. Hiroko Tabunoki and Ms. Midori Ohta for their invaluable help. This work was supported by grants from the Research on Intractable Diseases (H21-Nanchi-Ippan-201; H22-Nanchi-Ippan-136), the Ministry of Health, Labour and Welfare (MHLW), Japan and the High-Tech Research Center Project (S0801043) and the Grant-in-Aid (C22500322), the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan.

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Authors and Affiliations

  1. Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo, 204-8588, Japan

    Jun-ichi Satoh

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  1. Jun-ichi Satoh
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Correspondence to Jun-ichi Satoh .

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Editors and Affiliations

  1. Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA

    Asfar S. Azmi

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Satoh, Ji. (2012). Human MicroRNA Targetome Indicates a Specialized Role of MicroRNAs in Regulation of Oncogenesis. In: Azmi, A.S. (eds) Systems Biology in Cancer Research and Drug Discovery. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4819-4_10

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