MicroRNAs differentially expressed in ACTH-secreting pituitary tumors.
BACKGROUND
MicroRNAs (miRNAs) are small noncoding RNAs, functioning as antisense regulators of gene expression by targeting mRNA and contributing to cancer development and progression. More than 50% of miRNA genes are located in cancer-associated genomic regions or in fragile sites of the genome.


OBJECTIVE
The aim of the study was to analyze the differential expression of let-7a, miR-15a, miR-16, miR-21, miR-141, miR-143, miR-145, and miR-150 in corticotropinomas and normal pituitary tissue and verify whether their profile of expression correlates with tumor size or remission after treatment.


METHODS
ACTH-secreting pituitary tumor samples were obtained during transphenoidal surgery from patients with Cushing disease and normal pituitary tissues from autopsies. The relative expression of miRNAs was measured by real-time PCR using RNU44 and RNU49 as endogenous controls. Relative quantification of miRNA expression was calculated using the 2(-DeltaDeltaCt) method.


RESULTS
We found underexpression of miR-145 (2.0-fold; P = 0.04), miR-21 (2.4-fold; P = 0.004), miR-141 (2.6-fold; P = 0.02), let-7a (3.3-fold; P = 0.003), miR-150 (3.8-fold; P = 0.04), miR-15a (4.5-fold; P = 0.03), miR-16 (5.0-fold; P = 0.004), and miR-143 (6.4-fold; P = 0.004) in ACTH-secreting pituitary tumors when compared to normal pituitary tissues. There were no differences between miRNA expression and tumor size as well as miRNA expression and ratio of remission after surgery, except in patients presenting lower miR-141 expression who showed a better chance of remission.


CONCLUSIONS
Our results support the possibility that altered miRNA expression profile might be involved in corticotrophic tumorigenesis. However, the lack of knowledge about miRNA target genes postpones full understanding of the biological functions of down-regulated or up-regulated miRNAs in corticotropinomas.
Amaral
Fernando Colbari
FC
Department of Internal Medicine, School of Medicine of Ribeirao Preto, University of Sao Paulo, 14049-900 Ribeirao Preto, Sao Paulo, Brazil.
Torres
Natalia
N
Saggioro
Fabiano
F
Neder
Luciano
L
Machado
Hélio Rubens
HR
Silva
Wilson Araújo
WA
Moreira
Ayrton Custódio
AC
Castro
Margaret
M
D049913:ACTH-Secreting Pituitary Adenoma / Q000235:genetics*; D000236:Adenoma / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D008875:Middle Aged; D047748:Pituitary ACTH Hypersecretion / Q000235:genetics; D055815:Young Adult
D035683:MicroRNAs