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

Int J Oncol. 2022 Nov;61(5):140. doi: 10.3892/ijo.2022.5430. Epub 2022 Sep 28.


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.

Keywords: H19; adrenal cortical tumors; insulin‑like growth factor 2; microRNAs; mitochondrial respiratory complexes.

MeSH terms

  • Adrenal Cortex Neoplasms* / genetics
  • Adrenal Cortex Neoplasms* / pathology
  • Adrenocortical Adenoma* / metabolism
  • Adrenocortical Adenoma* / pathology
  • Adrenocortical Carcinoma* / genetics
  • Adrenocortical Carcinoma* / pathology
  • Electron Transport Complex I / metabolism
  • Humans
  • Insulin-Like Growth Factor II / genetics
  • Insulin-Like Growth Factor II / metabolism
  • MicroRNAs* / genetics
  • NAD / metabolism
  • Ubiquinone


  • IGF2 protein, human
  • MIRN675 microRNA, human
  • MicroRNAs
  • NAD
  • Ubiquinone
  • Insulin-Like Growth Factor II
  • Electron Transport Complex I

Grants and funding

The present study was supported by grants from the Swedish Research Council (2021-03006), the Swedish Cancer Society (20 0843 and 20 0859), the Cancer Society in Stockholm (201223), the Gustav V Jubilee Foundation (204103), the Stockholm County Council (RS 2019-1054) and Funds from Karolinska Institutet (2020-01851 and 2020-01768).