mir-17-92: a polycistronic oncomir with pleiotropic functions - PubMed (original) (raw)

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mir-17-92: a polycistronic oncomir with pleiotropic functions

Virginie Olive et al. Immunol Rev. 2013 May.

Abstract

Neoplastic transformation is caused by accumulation of genetic lesions that ultimately convert normal cells into tumor cells with uncontrolled proliferation and survival, unlimited replicative potential, and invasive growth. Emerging evidence has highlighted the functional importance of non-coding RNAs, particularly microRNAs (miRNAs), in the initiation and progression of tumor development. The mir-17-92 miRNA is among the best characterized miRNA oncogenes, whose genomic amplification or aberrant elevation are frequently observed in a variety of tumor types. Unlike protein-coding oncogenes, where one transcript produces one protein, mir-17-92 encodes a polycistronic miRNA transcript that yields six individual miRNA components. This unique gene structure, shared by many important miRNA oncogenes and tumor suppressors, underlies the unique functionality of mir-17-92 in a cell type and context-dependent manner. Recent functional dissection of mir-17-92 indicates that individual mir-17-92 components perform distinct biological functions, which collectively regulate multiple related cellular processes during development and disease. The structural complexity of mir-17-92 as a polycistronic miRNA oncogene, along with the complex mode of interactions among its components, constitutes the molecular basis for its unique functional complexity during normal and tumor development.

© 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

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Figures

Fig. 1

Fig. 1

mir-17-92 encodes a polycistronic miRNA oncogene. A. The gene structure of the mir-17-92 polycistron. mir-17-92 encodes a miRNA precursor that yields 6 mature miRNAs. Based on seed sequence homology, these six miRNAs belong to four miRNA families. Homologous miRNA components are indicated by the same color. B. mir-17-92 has two closely related homologues in mammals. The mir-106a-393 and mir-106b-25 clusters contain homologous miRNAs to a subset of mir-17-92 components with a conserved genome arrangement.

Fig. 2

Fig. 2

A diagram of possible regulatory mechanisms that collectively modulate the biological functions of the mir-17-92 polycistronic oncomir.

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