MicroRNA Expression Signature and Target Prediction in Familial and Sporadic Primary macronodular adrenal hyperplasia

Abstract Background: Primary macronodular adrenal hyperplasia (PMAH) is a rare cause of Cushing's syndrome, usually characterized by functioning adrenal macronodules and increased cortisol production.Methods: To screen and analyze the microRNA profile of PMAH, so as to elucidate the possible pathogenesis of the disease, MiRNA microarray was used to test the tissue samples from familial patients with PMAH , sporadic patients with PMAH and normal controls of other non-tumor adrenocortical tissues, to identify characteristic microRNAs expression signatures. Random selected miRNAs were validated by RT-PCR. Furthermore, the key signal pathways and miRNAs involved in PMAH pathogenesis were analyzed by gene ontology and pathway analysis.Results: Characteristic microRNA expression signatures were identified for familial patients with PMAH including 16 differentially expressed microRNAs and sporadic patients with PMAH including 8 differentially expressed microRNAs respectively. RT-PCR assay confirmed the chosed miRNAs expression, suggesting the high reliability of miRNA array. Pathway analysis showed that the most enriched pathway was renal cell carcinoma pathway. Overexpression of miR-17，miR-20a and miR-130b may be inhibit glucocorticoid-induced apoptosis in the PMAH pathogenesis.Conclusion: We have identified the miRNA signature in in Familial and Sporadic patients with PMAH, The differentially expressed miRNAs may be involved in the mechanisms of PMAH pathogenesis. Specific miRNAs, such as miR-17，miR-20a and miR-130b may be new potential targets for further functional studies of PMAH.