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 -