Global microRNA profiling of well-differentiated small intestinal neuroendocrine tumors

Abstract

Well-differentiated small intestinal neuroendocrine tumors are rare malignancies. They arise from enterochromaffin cells and very little is known about differential microRNA (miRNA) expression. The aim of this study was to identify the miRNA profile of well-differentiated small intestinal neuroendocrine tumors, which may have a critical role in tumor development, progression and potentially develop miRNAs as novel clinical biomarkers. Specimens from two test groups, 24 small intestinal neuroendocrine tumor specimens at different stages of malignancy, are included in this study. Total RNA from the first test group, five primary tumors, five mesentery metastases and five liver metastases was hybridized onto the Affymetrix Genechip miRNA arrays to perform a genome-wide profile. The results were validated by using quantitative real-time PCR (QRT-PCR) and northern blot analyses. We then expanded the investigation to laser capture microdissected small intestinal neuroendocrine tumor cells and immuno-laser capture microdissected normal enterochromaffin cells of the first test group. Furthermore, a second test group, three primary tumors, three mesentery metastases and three liver metastases, was included in the study. Thus, two independent test groups validated the data by QRT-PCR. Moreover, we characterized nine miRNAs, five (miR-96, -182, -183, -196a and -200a), which are upregulated during tumor progression, whereas four (miR-31, -129-5p, -133a and -215) are downregulated. Several online software programs were used to predict potential miRNA target genes to map a number of putative target genes for the aberrantly regulated miRNAs, through an advanced and novel bioinformatics analysis. Our findings provide information about pivotal miRNAs, which may lead to further insights into tumorigenesis, progression mechanisms and novel therapeutic targets recognition.

Keringő mikroRNS-ek az endokrin daganatok diagnosztikájában

“…A miR-1290 a hasnyálmirigy neuroendokrin tumoraiban fokozott expresszióját írták le, amely adenocarcinomától való differenciáldiagnózisban jelenthet segítséget (4. táb-lázat) [45]. Vékonybél neuroendokrin tumoros betegek szérumában felülexpresszálódást mutattak ki a miR-96, miR-182, miR-183, miR-196a és miR-200a esetén, míg a miR-31, miR-129-5p, miR-133a és miR-215 expreszsziója csökkent volt [46].…”

Molecular challenges of neuroendocrine tumors (Review)

“…Indeed, miR-183, -488, and 19a+b were upregulated while miR-133a, -145, 146, -222 and -10b were downregulated in metastatic tissue with respect to primary tumors in study with ileal carcinoid tumors (140). Intestinal NETs had different expression profiles of miRNA during different stages of the disease (141). Literature data suggests that miR-129-5p may have an anti-proliferative and anti-metastatic effect in midgut carcinoid tumors (142).…”

The future: diagnostic and imaging advances in MEN1 therapeutic approaches and management strategies

“…Li and coworkers characterized miRNA levels in well-differentiated small intestinal neuroendocrine tumors. The authors detected nine miRNAs: five (miR-96, -182, -183, -196a and -200a) were upregulated during tumor progression and the rest (miR-31, -129-5p, -133a and -215) were downregulated (Li et al 2013).…”