Imperial College London
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DrLeandroCastellano

Faculty of Medicine, Department of Surgery & Cancer

Visiting Reader
 
 
 
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Contact

 

+44 (0)20 7594 2822l.castellano Website

 
 
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Location

 

ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Miller:2016:10.1530/ERC-16-0044,
author = {Miller, HC and Frampton, AE and Malczewska, A and Ottaviani, S and Stronach, EA and Flora, R and Kaemmerer, D and Schwach, G and Pfragner, R and Faiz, O and Kos-Kuda, B and Hanna, GB and Stebbing, J and Castellano, L and Frilling, A},
doi = {10.1530/ERC-16-0044},
journal = {Endocrine-Related Cancer},
pages = {711--726},
title = {MicroRNAs associated with small bowel neuroendocrine tumours and their metastases},
url = {http://dx.doi.org/10.1530/ERC-16-0044},
volume = {23},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Miller,HC
AU  - Frampton,AE
AU  - Malczewska,A
AU  - Ottaviani,S
AU  - Stronach,EA
AU  - Flora,R
AU  - Kaemmerer,D
AU  - Schwach,G
AU  - Pfragner,R
AU  - Faiz,O
AU  - Kos-Kuda,B
AU  - Hanna,GB
AU  - Stebbing,J
AU  - Castellano,L
AU  - Frilling,A
DO  - 10.1530/ERC-16-0044
EP  - 726
PY  - 2016///
SN  - 1479-6821
SP  - 711
TI  - MicroRNAs associated with small bowel neuroendocrine tumours and their metastases
T2  - Endocrine-Related Cancer
UR  - http://dx.doi.org/10.1530/ERC-16-0044
UR  - http://hdl.handle.net/10044/1/34188
VL  - 23
ER  -
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