Open Access

Altered expression of the IGF2‑H19 locus and mitochondrial respiratory complexes in adrenocortical carcinoma

  • Authors:
    • Patrick Scicluna
    • Stefano Caramuta
    • Hanna Kjellin
    • Cheng Xu
    • Robin Fröbom
    • Monira Akhtar
    • Jiwei Gao
    • Hao Shi
    • Magnus Kjellman
    • Malin Almgren
    • Anders Höög
    • Jan Zedenius
    • Tomas J. Ekström
    • Robert Bränström
    • Weng-Onn Lui
    • Catharina Larsson
  • View Affiliations

  • Published online on: September 27, 2022     https://doi.org/10.3892/ijo.2022.5430
  • Article Number: 140
  • Copyright: © Scicluna et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.
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November-2022
Volume 61 Issue 5

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Online ISSN:1791-2423

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Spandidos Publications style
Scicluna P, Caramuta S, Kjellin H, Xu C, Fröbom R, Akhtar M, Gao J, Shi H, Kjellman M, Almgren M, Almgren M, et al: Altered expression of the <em>IGF2‑H19</em> locus and mitochondrial respiratory complexes in adrenocortical carcinoma. Int J Oncol 61: 140, 2022.
APA
Scicluna, P., Caramuta, S., Kjellin, H., Xu, C., Fröbom, R., Akhtar, M. ... Larsson, C. (2022). Altered expression of the <em>IGF2‑H19</em> locus and mitochondrial respiratory complexes in adrenocortical carcinoma. International Journal of Oncology, 61, 140. https://doi.org/10.3892/ijo.2022.5430
MLA
Scicluna, P., Caramuta, S., Kjellin, H., Xu, C., Fröbom, R., Akhtar, M., Gao, J., Shi, H., Kjellman, M., Almgren, M., Höög, A., Zedenius, J., Ekström, T. J., Bränström, R., Lui, W., Larsson, C."Altered expression of the <em>IGF2‑H19</em> locus and mitochondrial respiratory complexes in adrenocortical carcinoma". International Journal of Oncology 61.5 (2022): 140.
Chicago
Scicluna, P., Caramuta, S., Kjellin, H., Xu, C., Fröbom, R., Akhtar, M., Gao, J., Shi, H., Kjellman, M., Almgren, M., Höög, A., Zedenius, J., Ekström, T. J., Bränström, R., Lui, W., Larsson, C."Altered expression of the <em>IGF2‑H19</em> locus and mitochondrial respiratory complexes in adrenocortical carcinoma". International Journal of Oncology 61, no. 5 (2022): 140. https://doi.org/10.3892/ijo.2022.5430