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The role of microRNAs in cancers of the upper gastrointestinal tract

Nature Reviews Gastroenterology & Hepatology volume 10, pages 109–118 (2013)Cite this article

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Abstract

Cancers of the oesophagus, gastro-oesophageal junction and stomach (upper gastrointestinal tract cancers; UGICs) pose a major health risk around the world. Collectively, the 5-year survival rate has remained <15%, and therapeutic improvements have been very slow and small. Novel molecules for early diagnosis, prognosis and therapy are, therefore, urgently needed. The role that microRNA (miRNA) molecules have in UGICs are worth pursuing to this end. miRNAs are small noncoding RNA molecules that regulate ∼60% of coding genes in humans and, therefore, are pivotal in mediating and regulating many physiologic processes. miRNAs are deregulated in many disease states, particularly in cancer, making them important targets. Here, we review the growing body of evidence regarding the alterations of miRNAs in UGICs. By suppressing translation and/or promoting degradation of mRNAs, miRNAs can contribute to carcinogenesis and progression of UGICs. In-depth studies of miRNAs in UGICs might yield novel insights and potential novel therapeutic strategies.

Key Points

  • Cancers of the oesophagus, gastro-oesophageal junction and stomach (UGICs) are common worldwide, and outcomes for patients with these cancers have remained dismal

  • miRNAs are noncoding, single-stranded RNAs ∼22 nucleotides in length; they comprise a novel class of gene regulators that negatively regulate their targets

  • Many miRNA that act as oncogenes, tumour suppressors and important modulators in the process of invasion and metastasis of UGICs have been identified

  • Increased activity of oncogenic miRNAs leads to inhibition of tumour suppressor genes, facilitating cell proliferation and tumour progression; decreased activity of tumour-suppressor miRNAs leads to increased oncogene translation, contributing to tumour progression

  • Certain miRNAs are involved in the regulation of metastasis as well as in modulation of chemoresistance in UGICs

  • Circulating miRNAs provide potential biomarkers for early diagnosis and prognosis in patients with UGICs; further research could lead to exploitation of miRNAs as therapeutic or diagnostic targets for these cancers

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Figure 1: miRNAs, targets and functions in oesophageal cancers.
Figure 2: miRNAs, targets and functions in gastric cancer.

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Acknowledgements

This work was supported in part by the Dallas, Park, Smith, and Cantu family funds; the Kevin Fund; the Sultan Fund; the River Creek Foundation; and the Aaron and Martha Schecter Private Foundation. This work was also supported by the Multidisciplinary Research Program at The University of Texas MD Anderson Cancer Center and by the National Institutes of Health through MD Anderson Cancer Center Support Grants CA016672 and CA138671 (J.Ajani).

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Authors and Affiliations

  1. Department of Gastrointestinal Medical Oncology, 1515 Holcombe Boulevard, Houston, 77030, TX, USA

    Shumei Song

  2. Departments of Gastrointestinal Medical Oncology and Molecular Epidemiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, 77030, TX, USA

    Jaffer A. Ajani

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  1. Shumei Song
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  2. Jaffer A. Ajani
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Both authors contributed equally to all aspects of this manuscript.

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Correspondence to Jaffer A. Ajani.

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Song, S., Ajani, J. The role of microRNAs in cancers of the upper gastrointestinal tract. Nat Rev Gastroenterol Hepatol 10, 109–118 (2013). https://doi.org/10.1038/nrgastro.2012.210

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