MicroRNAs expressed during lung cancer development are expressed in human pseudoglandular lung embryogenesis.
OBJECTIVE
MicroRNAs (miRNAs) play a role during mouse embryonic development and are also important in carcinogenesis. In order to investigate whether there are similar patterns of miRNA expression levels in pseudoglandular human embryonic lung and in human lung tumors, we have analyzed 18 miRNAs (the let-7 family, the miR-17-92 cluster, miR-221 and miR-222) in human embryonic lung samples and in paired lung tumor and normal lung tissue samples and correlated the results with clinicopathological characteristics.


METHODS
RNA was obtained from 12 human embryonic lung samples, 33 lung tumor samples and 33 paired normal lung samples. miRNAs were assessed by quantitative real-time PCR.


RESULTS
Members of the let-7 family were downregulated and members of the miR-17-92 cluster and miR-221 were overexpressed both in embryonic lung tissue and in lung tumors. Low levels of let-7c were associated with absence of metastases (p = 0.015), early-stage non-small cell lung cancer (NSCLC, p = 0.05), and smokers (p = 0.009). High levels of miR-106a were associated with small-cell lung cancer (p = 0.031), and high levels of miR-19a with advanced NSCLC (p = 0.008).


CONCLUSIONS
Our study lends support to the model of cancer as an alteration of normal development, as many miRNAs were similarly expressed in early human lung development and stage I-II of lung cancer development.
Navarro
Alfons
A
Human Anatomy and Embryology, School of Medicine, University of Barcelona, Barcelona, Spain.
Marrades
Ramon M
RM
Viñolas
Nuria
N
Quera
Angels
A
Agustí
Carlos
C
Huerta
Arturo
A
Ramirez
Jose
J
Torres
Antoni
A
Monzo
Mariano
M
D000368:Aged; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008168:Lung / Q000196:embryology* / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D008875:Middle Aged; D016133:Polymerase Chain Reaction
D035683:MicroRNAs