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Expression of clock-related genes in benign and malignant adrenal tumors

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Abstract

Although the effect of the central clock system on adrenal function has been extensively studied, the role of the peripheral clock system in adrenal tumorigenesis remains largely unexplored. In this study we investigated the expression of clock-related genes in normal adrenocortical tissue and adrenocortical tumors. Twenty-seven fresh frozen human adrenal tissues including 13 cortisol secreting adenomas (CSA), seven aldosterone producing adenomas (APA), and seven adrenocortical carcinomas (ACC) were collected. CLOCK, BMAL1, PER1, CRY1, Rev-ERB, and RORα mRNA and protein expression were determined by qPCR and immunoblotting in pathological tissues and compared with the adjacent normal adrenal tissues. A significant downregulation of PER1, CRY1, and Rev-ERB compared with their normal tissue was demonstrated in CSA. All clock-related genes were overexpressed in APA compared with their normal tissue, albeit not significantly. A significant upregulation of CRY1 and PER1 and downregulation of BMAL1, RORα, and Rev-ERB compared with normal adrenal tissue was observed in ACC. BMAL1 and PER1 were significantly downregulated in APA compared with CSA. CLOCK, CRY1, and PER1 were upregulated, whereas BMAL1, RORα, and Rev-ERB were downregulated in ACC compared with CSA. Our study demonstrated the expression of CLOCK, BMAL1, PER1, CRY1, Rev-ERB, and RORα in normal and pathological human adrenal tissues. Adrenal tumors exhibited altered expression of these genes compared with normal tissue, with specific differences between benign and malignant lesions and between benign tumors arising from glomerulosa vs fasciculata zone. Further studies should clarify whether these alterations could be implicated in adrenocortical tumorigenesis.

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Author notes

  1. These authors contributed equally: Anna Angelous, Narjes Nasiri-Ansari

Authors and Affiliations

  1. 1st Department of Internal Medicine, Laiko University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    Anna Angelousi & Eva Kassi

  2. Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Goudi, 11527, Athens, Greece

    Narjes Nasiri-Ansari, Angeliki Karapanagioti, Georgios Kyriakopoulos, Athanasios G. Papavassiliou & Eva Kassi

  3. 3rd Department of Surgery, General Hospital of Athens “G. Gennimatas”, Athens, Greece

    Chrysanthi Aggeli, Giorgos Zografos & Christos Parianos

  4. Department of Pathology, General Hospital of Athens “G. Gennimatas”, Athens, Greece

    Theodosia Choreftaki

  5. Department of Endocrinology and Diabetes Center, Athens General Hospital “G. Gennimatas”, Athens, Greece

    Theodora Kounadi

  6. 1st Department of Propaedeutic Internal Medicine, Laiko University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    Krystallenia Alexandraki & Gregory Kaltsas

  7. Division of Translational and Experimental Medicine, Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK

    Harpal S. Randeva

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  1. Anna Angelousi
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Angelousi, A., Nasiri-Ansari, N., Karapanagioti, A. et al. Expression of clock-related genes in benign and malignant adrenal tumors. Endocrine 68, 650–659 (2020). https://doi.org/10.1007/s12020-020-02246-z

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