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Non-coding RNAs in GI cancers: from cancer hallmarks to clinical utility
  1. Mihnea Paul Dragomir1,
  2. Scott Kopetz2,
  3. Jaffer A Ajani2,
  4. George Adrian Calin1
  1. 1Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  2. 2Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  1. Correspondence to Dr George Adrian Calin, Experimental therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; gcalin{at}mdanderson.org

Abstract

One of the most unexpected discoveries in molecular oncology, in the last decades, was the identification of a new layer of protein coding gene regulation by transcripts that do not codify for proteins, the non-coding RNAs. These represent a heterogeneous category of transcripts that interact with many types of genetic elements, including regulatory DNAs, coding and other non-coding transcripts and directly to proteins. The final outcome, in the malignant context, is the regulation of any of the cancer hallmarks. Non-coding RNAs represent the most abundant type of hormones that contribute significantly to cell-to cell communication, revealing a complex interplay between tumour cells, tumour microenvironment cells and immune cells. Consequently, profiling their abundance in bodily fluids became a mainstream of biomarker identification. Therapeutic targeting of non-coding RNAs represents a new option for clinicians that is currently under development. This review will present the biology and translational value of three of the most studied categories on non-coding RNAs, the microRNAs, the long non-coding RNAs and the circular RNAs. We will also focus on some aspirational concepts that can help in the development of clinical applications related to non-coding RNAs, including using pyknons to discover new non-coding RNAs, targeting human-specific transcripts which are expressed specifically in the tumour cell and using non-coding RNAs to increase the efficiency of immunotherapy.

  • cancer genetics
  • gastric cancer
  • colorectal cancer
  • pancreatic cancer
  • hepatocellular carcinoma
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Footnotes

  • Contributors MPD and GAC developed the main concept of the manuscript. MPD, SK, JA and GAC wrote the manuscript.

  • Funding GAC is the Felix L. Haas Endowed Professor in Basic Science. Work in Dr. GAC’s laboratory is supported by National Institutes of Health (NIH/NCATS) grant UH3TR00943-01 through the NIH Common Fund, Office of Strategic Coordination (OSC), the NCI grants 1R01CA182905-01 and 1R01CA222007-01A1, an NIGMS 1R01GM122775-01 grant, a U54 grant #CA096297/CA096300—UPR/MDACC Partnership for Excellence in Cancer Research 2016 Pilot Project, a Team DOD (CA160445P1) grant, a Chronic Lymphocytic Leukemia Moonshot Flagship project, the UT MD Anderson Cancer Center Duncan Family Institute for Cancer Prevention and Risk Assessment, a Sister Institution Network Fund (SINF) 2017 grant and the Estate of C.G. Johnson, Jr. JAA is supported by US Department of Defense (DOD) grants CA160445. SK is supported by the NIH through Cancer Center Support Grant P30CA016672, R01CA187238 and R01CA172670.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Commissioned; externally peer reviewed.

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