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Junk DNA and the long non-coding RNA twist in cancer genetics

Oncogene volume 34, pages 5003–5011 (2015)Cite this article

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Abstract

The central dogma of molecular biology states that the flow of genetic information moves from DNA to RNA to protein. However, in the last decade this dogma has been challenged by new findings on non-coding RNAs (ncRNAs) such as microRNAs (miRNAs). More recently, long non-coding RNAs (lncRNAs) have attracted much attention due to their large number and biological significance. Many lncRNAs have been identified as mapping to regulatory elements including gene promoters and enhancers, ultraconserved regions and intergenic regions of protein-coding genes. Yet, the biological function and molecular mechanisms of lncRNA in human diseases in general and cancer in particular remain largely unknown. Data from the literature suggest that lncRNA, often via interaction with proteins, functions in specific genomic loci or use their own transcription loci for regulatory activity. In this review, we summarize recent findings supporting the importance of DNA loci in lncRNA function and the underlying molecular mechanisms via cis or trans regulation, and discuss their implications in cancer. In addition, we use the 8q24 genomic locus, a region containing interactive SNPs, DNA regulatory elements and lncRNAs, as an example to illustrate how single-nucleotide polymorphism (SNP) located within lncRNAs may be functionally associated with the individual’s susceptibility to cancer.

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Acknowledgements

HL is an Odyssey Fellow, and his work is supported in part by the Odyssey Program at The University of Texas MD Anderson Cancer Center. GAC is The Alan M. Gewirtz Leukemia & Lymphoma Society Scholar. Work in Dr Calin's laboratory is supported in part by the NIH/NCI grants 1UH2TR00943-01 and 1 R01 CA182905-01, the UT MD Anderson Cancer Center SPORE in Melanoma grant from NCI (P50 CA093459), Aim at Melanoma Foundation and the Miriam and Jim Mulva research funds, the Brain SPORE (2P50CA127001), the Center for radiation Oncology Research Project, the Center for Cancer Epigenetics Pilot project, a 2014 Knowledge GAP MDACC grant, a CLL Moonshot pilot project, the UT MD Anderson Cancer Center Duncan Family Institute for Cancer Prevention and Risk Assessment, a SINF grant in colon cancer, the Laura and John Arnold Foundation, the RGK Foundation and the Estate of C. G. Johnson, Jr. MP is supported by an Erwin-Schroedinger Scholarship of the Austrian Science Funds (project no. J3389-B23). IBN is a Fulbright Scholar at MD Anderson Cancer Center. FS was supported by NIH grants CA131301 and CA157749. We apologize to all colleagues whose work was not cited because of space restrictions.

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Authors and Affiliations

  1. Department of Experimental Therapeutics, MD Anderson Cancer Center, University of Texas, Houston, TX, USA

    H Ling, K Vincent, M Pichler, I Berindan-Neagoe & G A Calin

  2. Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands

    R Fodde

  3. Department of Immunology and Research Center for Functional Genomics, Biomedicine and Translational Medicine University of Medicine and Pharmacy ‘I. Hatieganu’, Cluj-Napoca, Romania

    I Berindan-Neagoe

  4. Department of Functional Genomics, The Oncology Institute Ion Chiricuta, Cluj-Napoca, Romania

    I Berindan-Neagoe

  5. Department of Pathology, Beth Israel Deaconess Medical Center, Harvard medical School, Boston, MA, USA

    F J Slack

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  1. H Ling
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  2. K Vincent
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Correspondence to G A Calin.

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Ling, H., Vincent, K., Pichler, M. et al. Junk DNA and the long non-coding RNA twist in cancer genetics. Oncogene 34, 5003–5011 (2015). https://doi.org/10.1038/onc.2014.456

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