Introduction: MicroRNAs (miRNA) are non-coding RNA molecules involved in the posttranscriptional regulation of gene expression. MiRNAs bind mRNA molecules at their 3′ untranslated regions and induce translational repression or target degradation. MiRNAs play important roles in the pathogenesis of several neoplasms. There are no reports, however, on the possible involvement of miRNAs in the pathogenesis of adrenocortical tumors.
Objective: To study simultaneous miRNA and mRNA expression patterns in normal, hormonally inactive, cortisol-secreting benign and malignant adrenocortical tissues (ACC), and to identify major pathogenetic pathways by bioinformatics analysis.
Methods: Thirty-two tissue samples were studied approved by the Ethical Committee of the Hungarian Health Council. MiRNA and mRNA expression profiling was performed in 16 samples by TLDA Human MiR Panel and whole genome microarray platform, respectively. Results were further validated and sample sizes were extended by qRT-PCR. Tissue-specific miRNA target prediction was achieved by an integrative bioinformatics method. Ingenuity Pathway Analysis (IPA) was used as a system biology approach.
Results: Twenty-six miRNAs with significant expressional differences were identified. Further validation was performed for 14 miRNAs. Expression of miR-214, miR-375 and miR-511 were significantly lower, whereas that of miR-184, miR-210 and miR-503 was significantly higher in ACCs in comparison with their normal and benign counterparts. By performing parallel mRNA expression profiling, we tried to achieve a tissue specific target prediction approach. Pathway analysis of the predicted targets with inverse expressional alterations as compared with their potential regulator miRNA revealed the possible involvement of cell cycle damage at G2/M checkpoint (CDC25, RPRM), along with already described mechanisms (e.g. TOP2A, CCNB2) in the pathomechanism of ACC.
Discussion: MiRNA expression patterns are significantly different in normal and neoplastic adrenocortical tissues. Beside their possible pathogenetic relevance, miRNA patterns may also be exploited in diagnostics, e.g. as an adjunct to histological diagnostics or for the determination of prognosis.