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Non-coding RNA networks in cancer

Nature Reviews Cancer volume 18, pages 5–18 (2018)Cite this article

Subjects

Key Points

  • Non-coding RNAs (ncRNAs) participate in complex networks of interactions with other nucleic acids and proteins that often have wide-reaching effects on cell biology.

  • The mechanisms by which ncRNAs work and/or function are routinely dysregulated in various cancers.

  • Dysregulation of ncRNA interactions within cancer molecular pathways contributes to cancer and reveals important new targets for intervention.

  • In cancer, disruptions in ncRNA networks often do not involve just mutations that cause a gross gain-of-function or loss-of-function of a given ncRNA but can also involve mutations that change the sequence and downstream targets of that ncRNA.

Abstract

Thousands of unique non-coding RNA (ncRNA) sequences exist within cells. Work from the past decade has altered our perception of ncRNAs from 'junk' transcriptional products to functional regulatory molecules that mediate cellular processes including chromatin remodelling, transcription, post-transcriptional modifications and signal transduction. The networks in which ncRNAs engage can influence numerous molecular targets to drive specific cell biological responses and fates. Consequently, ncRNAs act as key regulators of physiological programmes in developmental and disease contexts. Particularly relevant in cancer, ncRNAs have been identified as oncogenic drivers and tumour suppressors in every major cancer type. Thus, a deeper understanding of the complex networks of interactions that ncRNAs coordinate would provide a unique opportunity to design better therapeutic interventions.

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Figure 1: Motifs in RNA networks.
Figure 2: Recurrent patterns of ncRNA function in cancer networks.
Figure 3: Putative functions of circular RNAs in cancer.
Figure 4: Adenosine-to-inosine editing of a tumour-suppressor gene or an oncogene.

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Acknowledgements

The authors thank A. L. Jiao and P. Trivedi for helpful comments on this manuscript. The authors acknowledge support from the Ludwig Center at Harvard, Boston, Massachusetts, USA, and grants from the US National Institutes of Health (R01 CA157749; P50 CA177444).

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Author notes

  1. Eleni Anastasiadou and Leni S. Jacob: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, Harvard Medical School Initiative for RNA Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, 02215, Massachusetts, USA

    Eleni Anastasiadou, Leni S. Jacob & Frank J. Slack

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  1. Eleni Anastasiadou
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  3. Frank J. Slack
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Contributions

E.A. and L.S.J. researched the data for the article. E.A., L.S.J. and F.J.S. provided substantial contributions to discussions of its content, wrote the article and undertook review and/or editing of the manuscript before submission.

Corresponding author

Correspondence to Frank J. Slack.

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Competing interests

F.J.S. is a founder and adviser to Mira Dx and 28/7 Rx. The other authors have no conflict of interest.

PowerPoint slides

Glossary

Network motifs

Patterns of interactions between nodes in a network that occur more often than by chance.

Supergene

A locus that produces multiple functional RNAs.

Endogenous small interfering RNAs

(Endo-siRNAs). Small RNAs that, unlike microRNAs, are derived from perfectly complementary sense–antisense RNA hybrids (double-stranded RNA).

Mirtrons

MicroRNAs derived from short hairpin introns and processed by the splicing machinery but not by ribonuclease 3 (Drosha).

Pseudogene

A nucleotide sequence that resembles a gene but does not lead to any protein expression.

Nuclear paraspeckles

Nuclear domains within interchromatin spaces, enriched in RNA processing factors.

Crosslinking immunoprecipitation followed by sequencing

(CLIP-seq). A method to study RNA–protein interactions by ultraviolet crosslinking followed by immunoprecipitation.

Staufen1-mediated mRNA decay

(SMD). A process that degrades mRNA through binding of double-stranded RNA-binding protein Staufen homologue 1 (STAU1) to its binding site in the 3′ untranslated regions of target mRNA.

Alu element

A short interspersed element, 300 bp in length, that is repeated in the human genome and forms a characteristic double-stranded RNA embedded in the precursor mRNA.

Alternative polyadenylation signals

When more than one site within a gene locus codes for the signal that allows a string of adenosine bases (poly(A) tail) to be added to the end of the transcript.

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Anastasiadou, E., Jacob, L. & Slack, F. Non-coding RNA networks in cancer. Nat Rev Cancer 18, 5–18 (2018). https://doi.org/10.1038/nrc.2017.99

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