Small Molecules in Rare Tumors: Emerging Role of MicroRNAs in GIST

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Abstract

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of gastrointestinal tract. GISTs have very different clinical phenotypes and underlying molecular characteristics that are not yet completely understood. microRNAs (miRNAs) have been shown to participate in carcinogenesis pathways through post-transcriptional regulation of gene expression in different tumors. Over the last years emerging evidence has highlighted the role of miRNAs in GISTs. This review provides an overview of original research papers that analyze miRNA deregulation patterns, functional role, diagnostic, therapeutic and prognostic implications in GIST as well as provides directions for further research in the field.

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Most cited references 69

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PDGFRA activating mutations in gastrointestinal stromal tumors.

Michael Heinrich, Christopher L Corless, Anette Duensing … (2003)

Most gastrointestinal stromal tumors (GISTs) have activating mutations in the KIT receptor tyrosine kinase, and most patients with GISTs respond well to Gleevec, which inhibits KIT kinase activity. Here we show that approximately 35% (14 of 40) of GISTs lacking KIT mutations have intragenic activation mutations in the related receptor tyrosine kinase, platelet-derived growth factor receptor alpha (PDGFRA). Tumors expressing KIT or PDGFRA oncoproteins were indistinguishable with respect to activation of downstream signaling intermediates and cytogenetic changes associated with tumor progression. Thus, KIT and PDGFRA mutations appear to be alternative and mutually exclusive oncogenic mechanisms in GISTs.

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The microcosmos of cancer.

Amaia Lujambio, Scott Lowe (2012)

The discovery of microRNAs (miRNAs) almost two decades ago established a new paradigm of gene regulation. During the past ten years these tiny non-coding RNAs have been linked to virtually all known physiological and pathological processes, including cancer. In the same way as certain key protein-coding genes, miRNAs can be deregulated in cancer, in which they can function as a group to mark differentiation states or individually as bona fide oncogenes or tumour suppressors. Importantly, miRNA biology can be harnessed experimentally to investigate cancer phenotypes or used therapeutically as a target for drugs or as the drug itself.

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Target RNA-directed trimming and tailing of small silencing RNAs.

Stefan Ameres, Michael D Horwich, Jui-Hung Hung … (2010)

In Drosophila, microRNAs (miRNAs) typically guide Argonaute1 to repress messenger RNA (mRNA), whereas small interfering RNAs (siRNAs) guide Argonaute2 to destroy viral and transposon RNA. Unlike siRNAs, miRNAs rarely form extensive numbers of base pairs to the mRNAs they regulate. We find that extensive complementarity between a target RNA and an Argonaute1-bound miRNA triggers miRNA tailing and 3'-to-5' trimming. In flies, Argonaute2-bound small RNAs--but not those bound to Argonaute1--bear a 2'-O-methyl group at their 3' ends. This modification blocks target-directed small RNA remodeling: In flies lacking Hen1, the enzyme that adds the 2'-O-methyl group, Argonaute2-associated siRNAs are tailed and trimmed. Target complementarity also affects small RNA stability in human cells. These results provide an explanation for the partial complementarity between animal miRNAs and their targets.

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Journal

Journal ID (nlm-ta): Int J Mol Sci

Journal ID (iso-abbrev): Int J Mol Sci

Journal ID (publisher-id): ijms

Title: International Journal of Molecular Sciences

Publisher: MDPI

ISSN (Electronic): 1422-0067

Publication date (Electronic): 30 January 2018

Publication date Collection: February 2018

Volume: 19

Issue: 2

Electronic Location Identifier: 397

Affiliations

[1 ]Institute for Digestive Research, Academy of Medicine, Lithuanian University of Health Sciences, Eiveniu str. 2, LT-50009 Kaunas, Lithuania; juozas.kupcinskas@ 123456lsmuni.lt ; Tel.: +370-37-326898

[2 ]Department of Gastroenterology, Academy of Medicine, Lithuanian University of Health Sciences, Eiveniu str. 2, LT-50009 Kaunas, Lithuania

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Juozas Kupcinskas https://orcid.org/0000-0002-8760-7416

Article

Publisher ID: ijms-19-00397

DOI: 10.3390/ijms19020397

PMC ID: 5855619

PubMed ID: 29385688

SO-VID: c723c331-f917-490b-8a8b-625891d5b8db

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Small Molecules in Rare Tumors: Emerging Role of MicroRNAs in GIST

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Entomologia Generalis

Most cited references 69

PDGFRA activating mutations in gastrointestinal stromal tumors.

The microcosmos of cancer.

Target RNA-directed trimming and tailing of small silencing RNAs.

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