Spindle cell oncocytomas (SCO) of the pituitary are rare
tumors accounting for 0.1-0.4% of all sellar
tumors. Due to their rarity, little information is available regarding their pathogenesis. Our aim was to investigate
miRNA expression profile of pituitary oncocytomas. Total
RNA was extracted from 9
formalin-fixed
paraffin embedded pituitary samples (4 primary, 3 recurrent oncocytomas and 2 normal tissues). Next-generation sequencing was performed for
miRNA profiling. Transcriptome data of additional 6 samples' were obtained from NBCI GEO database for gene expression reanalysis and tissue-specific target prediction. Bioinformatical analysis, in vitro
miRNA mimics transfection,
luciferase reporter system and
AlamarBlue assay were applied to characterize
miRNA's function. 54 differentially expressed
miRNAs and 485 genes in pituitary SCO vs. normal tissue and 8
miRNAs in recurrent vs. primary SCO were determined. Global
miRNA downregulation and decreased level of DROSHA were detected in SCO samples vs. normal tissue. Transcriptome analysis revealed cell cycle alterations while
miRNAs influenced mainly metabolic processes (tricarboxylic acid cycle-TCA,
carbohydrate, lipid metabolism). Through
miRNA-target interaction network the overexpressed
Aconitase 2 potentially targeted by two downregulated
miRNAs (miR-744-5p, miR-127-3p) was revealed. ACO2 and miR-744-5p interaction was validated by
luciferase assay. MiR-127-3p and miR-744-5p significantly decreased cell proliferation in vitro. Our study firstly reported
miRNA profile of pituitary
oncocytoma. Our results suggest that
tumor suppressor
miRNAs may have an essential role in the pathogenesis of pituitary
oncocytoma. Earlier reports showed downregulated TCA cycle in SCO which is extended by our results adding the role of miR-744-5p targeting ACO2.