Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
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.
MicroRNAs associated with small bowel neuroendocrine tumours and their metastases.
Endocr Relat Cancer. 2016; 23(9):711-726
Doi: 10.1530/ERC-16-0044
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- Co-authors Med Uni Graz
- Pfragner Roswitha
- Schwach Gert
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- 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. © 2016 Society for Endocrinology.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Aged, 80 and over -
- Biomarkers, Tumor - genetics
- Humans -
- Intestinal Neoplasms - genetics
- Intestinal Neoplasms - pathology
- Liver - metabolism
- Liver Neoplasms - genetics
- Liver Neoplasms - secondary
- Lymph Nodes - metabolism
- Lymphatic Metastasis - genetics
- MicroRNAs -
- Middle Aged -
- Neuroendocrine Tumors - genetics
- Neuroendocrine Tumors - pathology
- Find related publications in this database (Keywords)
- microRNAs
- small bowel
- neuroendocrine tumour
- biomarkers
- metastasis