TY - JOUR AB - Abnormalities of the insulin‑like growth factor 2 (IGF2)‑H19 locus with the overexpression of IGF2 are frequent findings in adrenocortical carcinoma (ACC). The present study assessed the expression of RNAs and microRNAs (miRNAs/miRs) from the IGF2‑H19 locus using PCR‑based methods in ACC and adrenocortical adenoma (ACA). The results were associated with proteomics data. IGF2 was overexpressed in ACC, and its expression correlated with that of miR‑483‑3p and miR‑483‑5p hosted by IGF2. The downregulated expression of H19 in ACC compared to ACA correlated with miR‑675 expression hosted by H19. Several proteins exhibited an inverse correlation in expression and were predicted as targets of miR‑483‑3p, miR‑483‑5p or miR‑675. 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 miR‑483‑5p 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 IGF2‑H19 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. AD - Department of Oncology‑Pathology, BioClinicum, Karolinska University Hospital, Karolinska Institutet, SE‑171 64 Solna, Sweden Department of Molecular Medicine and Surgery, Karolinska Institutet, SE‑171 76 Stockholm, Sweden Department of Clinical Neuroscience, Karolinska Institutet, SE‑171 76 Stockholm, Sweden AU - Scicluna,Patrick AU - Caramuta,Stefano AU - Kjellin,Hanna AU - Xu,Cheng AU - Fröbom,Robin AU - Akhtar,Monira AU - Gao,Jiwei AU - Shi,Hao AU - Kjellman,Magnus AU - Almgren,Malin AU - Höög,Anders AU - Zedenius,Jan AU - Ekström,Tomas,J. AU - Bränström,Robert AU - Lui,Weng-Onn AU - Larsson,Catharina DA - 2022/11/01 DO - 10.3892/ijo.2022.5430 IS - 5 JO - Int J Oncol KW - adrenal cortical tumors insulin‑like growth factor 2 H19 microRNAs mitochondrial respiratory complexes PY - 2022 SN - 1019-6439 1791-2423 SP - 140 ST - Altered expression of the IGF2‑H19 locus and mitochondrial respiratory complexes in adrenocortical carcinoma T2 - International Journal of Oncology TI - Altered expression of the IGF2‑H19 locus and mitochondrial respiratory complexes in adrenocortical carcinoma UR - https://doi.org/10.3892/ijo.2022.5430 VL - 61 ER -