MicroRNAs associated with small bowel neuroendocrine tumours and their metastases
| Autor: | Gerd Schwach, Euan A. Stronach, Daniel Kaemmerer, Silvia Ottaviani, Beata Kos-Kudła, Justin Stebbing, Adam E Frampton, George B. Hanna, Rashpal Flora, Helen C Miller, Leandro Castellano, Anna Malczewska, Omar Faiz, Andrea Frilling, Roswitha Pfragner |
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| Přispěvatelé: | Commission of the European Communities, National Institute for Health Research, The UK and Ireland Neuroendocrine Tumour Society (UKI NETS) |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Endocrinology Diabetes and Metabolism Disease Neuroendocrine tumors Bioinformatics Metastasis 0302 clinical medicine Endocrinology small bowel neuroendocrine tumour small bowel neuroendocrine tumour Lymph node Aged 80 and over Medical And Health Sciences Liver Neoplasms Middle Aged Biological Sciences microRNAs Neuroendocrine Tumors medicine.anatomical_structure Liver Oncology Lymphatic Metastasis 030220 oncology & carcinogenesis Life Sciences & Biomedicine mirna FOSB Adult Treatment response Biology Endocrinology & Metabolism 03 medical and health sciences Downregulation and upregulation Intestinal Neoplasms microRNA Biomarkers Tumor medicine Humans metastasis Oncology & Carcinogenesis Gene Aged Science & Technology business.industry Neurosciences biomarkers 1103 Clinical Sciences medicine.disease 030104 developmental biology Potential biomarkers Cancer research Lymph Nodes Neurosciences & Neurology business 1109 Neurosciences |
| Zdroj: | 14th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease |
| ISSN: | 1479-6821 1351-0088 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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