Identification of MicroRNAs Differentially Expressed in Lung Carcinoid Subtypes and Progression.

Abstract:

AIM:To extensively explore microRNA expression profiles in lung carcinoids in correlation with clinical and pathological features. METHODS:A PCR-based array was employed in the screening phase to analyze 752 microRNAs in a discovery set of 12 lung carcinoids, including 6 typical (3 with lymph node metastasis) and 6 atypical (3 with lymph node metastasis). The results were validated by means of real-time PCR in 37 carcinoids, including 22 typical (4 with lymph node metastasis) and 15 atypical (7 with lymph node metastasis), and 19 high-grade neuroendocrine carcinomas. RESULTS:Unsupervised cluster analysis segregated the pilot cases into 3 distinct groups. Twenty-four microRNAs were differentially regulated in atypical versus typical carcinoids, and 29 in metastatic versus nonmetastatic cases. Eleven microRNAs were selected for validation. All but 1 were significantly different among lung neuroendocrine tumor histotypes. Moreover, 5 (miR-129-5p, miR-409-3p, miR-409-5p, miR-185 and miR-497) were significantly upregulated in typical compared to atypical carcinoids. MiR-409-3p, miR-409-5p and miR-431-5p were also significantly downregulated in carcinoids metastatic to the lymph nodes. Predictive in silico analysis of specific target genes showed that these 3 latter microRNAs linked to metastatic potential are implicated in several cellular functions and highlighted several novel genes which may be worth exploring. CONCLUSIONS:Our findings demonstrate that lung carcinoids have distinct microRNA expression profiles as compared to high-grade neuroendocrine carcinomas and that specific microRNAs might have potential implications as diagnostic tools or clinical biomarkers.

journal_name

Neuroendocrinology

journal_title

Neuroendocrinology

authors

Rapa I,Votta A,Felice B,Righi L,Giorcelli J,Scarpa A,Speel EJ,Scagliotti GV,Papotti M,Volante M

doi

10.1159/000381454

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

246-55

issue

3

eissn

0028-3835

issn

1423-0194

pii

000381454

journal_volume

101

pub_type

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