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The microRNAs within the DLK1-DIO3 genomic region: involvement in disease pathogenesis

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Abstract

The mammalian genome is transcribed in a developmentally regulated manner, generating RNA strands ranging from long to short non-coding RNA (ncRNAs). NcRNAs generated by intergenic sequences and protein-coding loci, represent up to 98 % of the human transcriptome. Non-coding transcripts comprise short ncRNAs such as microRNAs, piwi-interacting RNAs, small nucleolar RNAs and long intergenic RNAs, most of which exercise a strictly controlled negative regulation of expression of protein-coding genes. In humans, the DLK1-DIO3 genomic region, located on human chromosome 14 (14q32) contains the paternally expressed imprinted genes DLK1, RTL1, and DIO3 and the maternally expressed imprinted genes MEG3 (Gtl2), MEG8 (RIAN), and antisense RTL1 (asRTL1). This region hosts, in addition to two long intergenic RNAs, the MEG3 and MEG8, one of the largest microRNA clusters in the genome, with 53 miRNAs in the forward strand and one (mir-1247) in the reverse strand. Many of these miRNAs are differentially expressed in several pathologic processes and various cancers. A better understanding of the pathophysiologic importance of the DLK1-DIO3 domain-containing microRNA cluster may contribute to innovative therapeutic strategies in a range of diseases. Here we present an in-depth review of this vital genomic region, and examine the role the microRNAs of this region may play in controlling tissue homeostasis and in the pathogenesis of some human diseases, mostly cancer, when aberrantly expressed. The potential clinical implications of this data are also discussed.

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Acknowledgments

E.H. is a scholar of the Hellenic Society of Haematology Foundation. P.L. and I.R. are partially supported by a William M. Keck Foundation grant.

Conflict of interest

The authors declare no potential conflicts of interest.

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Authors and Affiliations

  1. Transfusion Unit, General Hospital of Preveza, Selefkias 2, 48100, Preveza, Greece

    Leonidas Benetatos

  2. Department of Hematology, University Hospital of Ioannina, Ioannina, Greece

    Eleftheria Hatzimichael & Evangelos Briasoulis

  3. Cancer Biobank Center, University of Ioannina, Ioannina, Greece

    Eleftheria Hatzimichael & Evangelos Briasoulis

  4. Computational Medicine Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA

    Eleftheria Hatzimichael, Eric Londin, Phillipe Loher & Isidore Rigoutsos

  5. Molecular Biology Laboratory, University Hospital of Ioannina, Ioannina, Greece

    George Vartholomatos

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  6. Isidore Rigoutsos
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  7. Evangelos Briasoulis
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Corresponding author

Correspondence to Leonidas Benetatos.

Additional information

L. Benetatos, E. Hatzimichael contributed equally to this work.

I. Rigoutsos and E. Briasoulis contributed equally to this work.

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Benetatos, L., Hatzimichael, E., Londin, E. et al. The microRNAs within the DLK1-DIO3 genomic region: involvement in disease pathogenesis. Cell. Mol. Life Sci. 70, 795–814 (2013). https://doi.org/10.1007/s00018-012-1080-8

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  • DOI: https://doi.org/10.1007/s00018-012-1080-8

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