Altered expression of the IGF2H19 locus and mitochondrial respiratory complexes in adrenocortical carcinoma.
Int J Oncol
; 61(5)2022 Nov.
Article
en En
| MEDLINE
| ID: mdl-36169175
ABSTRACT
Abnormalities of the insulinlike 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 IGF2H19 locus using PCRbased 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 miR4833p and miR4835p hosted by IGF2. The downregulated expression of H19 in ACC compared to ACA correlated with miR675 expression hosted by H19. Several proteins exhibited an inverse correlation in expression and were predicted as targets of miR4833p, miR4835p or miR675. 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 NADHubiquinone 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 miR4835p 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 IGF2H19 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Corteza Suprarrenal
/
Carcinoma Corticosuprarrenal
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Adenoma Corticosuprarrenal
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MicroARNs
Límite:
Humans
Idioma:
En
Revista:
Int J Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2022
Tipo del documento:
Article
País de afiliación:
Suecia