Background: Primary macronodular adrenal hyperplasia (PMAH), previously termed ACTH-independent macronodular adrenal hyperplasia (AIMAH), is a rare cause of Cushing's syndrome usually characterized by functioning adrenal macronodules and increased cortisol production.
Methods: To screen and analyse the microRNA (miRNA) profile of PMAH in order to elucidate its possible pathogenesis, a miRNA microarray was used to test tissue samples from patients with familial PMAH, patients with sporadic PMAH and normal control samples of other nontumour adrenocortical tissues and identify characteristic microRNA expression signatures. Randomly selected miRNAs were validated by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Furthermore, the key signalling pathways and miRNAs involved in PMAH pathogenesis were determined by gene ontology and pathway analysis.
Results: Characteristic microRNA expression signatures were identified for patients with familial PMAH (16 differentially expressed microRNAs) and patients with sporadic PMAH (8 differentially expressed microRNAs). The expression of the selected miRNAs was confirmed by qRT-PCR, suggesting the high reliability of the miRNA array analysis results. Pathway analysis showed that the most enriched pathway was the renal cell carcinoma pathway. Overexpression of miR-17, miR-20a and miR-130b may inhibit glucocorticoid-induced apoptosis in PMAH pathogenesis.
Conclusion: We identified the miRNA signatures in patients with familial and sporadic 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 targets for further functional studies of PMAH.
Keywords: Familial; Pathogenesis; Pathway analysis; Primary macronodular adrenal hyperplasia (PMAH); Sporadic; microRNA expression.
© 2021. The Author(s).