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MicroRNAs associated with small bowel neuroendocrine tumours and their metastases

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Title: MicroRNAs associated with small bowel neuroendocrine tumours and their metastases
Authors: Miller, HC
Frampton, AE
Malczewska, A
Ottaviani, S
Stronach, EA
Flora, R
Kaemmerer, D
Schwach, G
Pfragner, R
Faiz, O
Kos-Kudła, B
Hanna, GB
Stebbing, J
Castellano, L
Frilling, A
Item Type: Journal Article
Abstract: Novel molecular analytes are needed in small bowel neuroendocrine tumours (SBNETs) to better determine disease aggressiveness and predict treatment response. In this study, we aimed to profile the global miRNome of SBNETs, and identify microRNAs (miRNAs) involved in tumour progression for use as potential biomarkers. Two independent miRNA profiling experiments were performed (n=90), including primary SBNETs (n=28), adjacent normal small bowel (NSB; n=14), matched lymph node (LN) metastases (n=24), normal LNs (n=7), normal liver (n=2) and liver metastases (n=15). We then evaluated potentially targeted genes by performing integrated computational analyses. We discovered 39 miRNAs significantly deregulated in SBNETs compared with adjacent NSB. The most upregulated (miR-204-5p, miR-7-5p and miR-375) were confirmed by qRT-PCR. Two miRNAs (miR-1 and miR-143-3p) were significantly downregulated in LN and liver metastases compared with primary tumours. Furthermore, we identified upregulated gene targets for miR-1 and miR-143-3p in an existing SBNET dataset, which could contribute to disease progression, and show that these miRNAs directly regulate FOSB and NUAK2 oncogenes. Our study represents the largest global miRNA profiling of SBNETs using matched primary tumour and metastatic samples. We revealed novel miRNAs deregulated during SBNET disease progression, and important miRNA–mRNA interactions. These miRNAs have the potential to act as biomarkers for patient stratification and may also be able to guide treatment decisions. Further experiments to define molecular mechanisms and validate these miRNAs in larger tissue cohorts and in biofluids are now warranted.
Issue Date: 15-Aug-2016
Date of Acceptance: 27-Jun-2016
URI: http://hdl.handle.net/10044/1/34188
DOI: http://dx.doi.org/10.1530/ERC-16-0044
ISSN: 1479-6821
Publisher: BioScientifica
Start Page: 711
End Page: 726
Journal / Book Title: Endocrine-Related Cancer
Volume: 23
Issue: 9
Copyright Statement: © 2016 Society for Endocrinology. Disclaimer: this is not the definitive version of record of this article. This manuscript has been accepted for publication in Endocrine-Related Cancer, but the version presented here has not yet been copy-edited, formatted or proofed. Consequently, Bioscientifica accepts no responsibility for any errors or omissions it may contain. The definitive version is now freely available at http://dx.doi.org/10.1530/ERC-16-0044.
Sponsor/Funder: Commission of the European Communities
National Institute for Health Research
The UK and Ireland Neuroendocrine Tumour Society (UKI NETS)
Funder's Grant Number: 300586
Keywords: biomarkers
neuroendocrine tumour
small bowel
Oncology & Carcinogenesis
Medical And Health Sciences
Biological Sciences
Publication Status: Published
Appears in Collections:Department of Surgery and Cancer