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What is the role of CHCHD2 in adrenal tumourigenesis?

Angeliki Karapanagioti1,2, Narjes Nasiri-Ansari1, Athanasios Moustogiannis3

  • 1Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Endocrine
|May 23, 2023
PubMed
Abstract

Insights

The mitochondrial protein CHCHD2 is upregulated in benign adrenal tumors but downregulated in carcinomas. Its absence increases cancer cell apoptosis, suggesting CHCHD2 as a potential therapeutic target in adrenal tumorigenesis.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • The antiapoptotic mitochondrial protein CHCHD2 (coiled-coil-helix-domain-containing protein 2) plays a role in the BCL2/BAX pathway in various cancers.
  • Data regarding the specific role of CHCHD2 in adrenal gland tumor development (adrenal tumourigenesis) are limited.

Purpose of the Study:

  • To investigate the expression of CHCHD2 and its association with BCL2 and BAX in human adrenocortical tissues.
  • To explore the functional impact of CHCHD2 on adrenal cancer cell behavior in vitro.

Main Methods:

  • Quantitative PCR (qPCR) and immunoblotting were used to analyze mRNA and protein levels of CHCHD2, BCL2, and BAX.
  • Expression analysis was performed on human benign adrenocortical neoplasms (BANs), adrenocortical carcinomas (ACCs), and adjacent normal adrenal tissues.
  • In vitro studies involved CHCHD2 gene silencing in SW13 cells, followed by assays for cell viability, apoptosis, and invasion.

Main Results:

  • CHCHD2 and BCL2 mRNA and protein levels were elevated in BANs compared to normal tissues, while BAX was decreased.
  • In ACCs, both BAX and CHCHD2 showed significant downregulation and upregulation, respectively, compared to BANs and controls.
  • CHCHD2 silencing in SW13 cells led to decreased cell viability and invasion, alongside increased apoptosis.

Conclusions:

  • CHCHD2 expression appears to be involved in adrenal tumourigenesis.
  • The absence of CHCHD2 promotes apoptosis in adrenal cancer cells in vitro.
  • Further research is needed to elucidate the precise mechanism of CHCHD2 action, particularly its interaction with the BAX/BCL2 pathway, to assess its potential as a therapeutic target.
Keywords:
Adrenal adenomasAdrenocortical carcinomaApoptosisBAXBCL2CHCHD2

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