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
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