Altered Expression of the Locus and Mitochondrial Respiratory Complexes in Adrenocortical Carcinoma

Abnormalities of the insulin‑like growth factor 2 locus with the overexpression of are frequent findings in adrenocortical carcinoma (ACC). The present study assessed the expression of RNAs and microRNAs (miRNAs/miRs) from the locus using PCR‑based methods in ACC and adrenocortical adenoma (ACA). The results were associated with proteomics data. was overexpressed in ACC, and its expression correlated with that of and hosted by . The downregulated expression of in ACC compared to ACA correlated with expression hosted by . Several proteins exhibited an inverse correlation in expression and were predicted as targets of , or . Subsets of these proteins were differentially expressed between ACC and ACA. These included several proteins involved in mitochondrial metabolism. Among the mitochondrial respiratory complexes, complex I and IV were significantly decreased in ACC compared to ACA. The protein expression of NADH:ubiquinone oxidoreductase subunit C1 (NDUFC1), a subunit of mitochondrial respiratory complex I, was further validated as being lower in ACC compared to ACA and normal adrenals. The silencing of increased NDUFC1 protein expression and reduced both oxygen consumption and glycolysis rates. On the whole, the findings of the present study reveal the dysregulation of the locus and mitochondrial respiration in ACC. These findings may provide a basis for the further understanding of the pathogenesis of ACC and may have potential values for diagnostics and treatment.