Non-coding RNAs in GI cancers: from cancer hallmarks to clinical utility

Gut. 2020 Apr;69(4):748-763. doi: 10.1136/gutjnl-2019-318279. Epub 2020 Feb 7.

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.

Keywords: cancer genetics; colorectal cancer; gastric cancer; hepatocellular carcinoma; pancreatic cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Gastrointestinal Neoplasms / genetics*
  • Gastrointestinal Neoplasms / pathology*
  • Gastrointestinal Neoplasms / therapy
  • Humans
  • MicroRNAs / physiology
  • RNA, Long Noncoding / physiology*

Substances

  • MicroRNAs
  • RNA, Long Noncoding