What is the role of CHCHD2 in adrenal tumourigenesis?

Abstract

Purpose CHCHD2 is an anti-apoptotic mitochondrial protein acting through the BCL2/BAX pathway in various cancers. However, data on the regulatory role of CHCHD2 in adrenal tumourigenesis are scarce. Methods We studied the expression of CHCHD2, BCL2 and BAX in human adrenocortical tissues and SW-13 cells. mRNA and protein levels were analysed through qPCR and immunoblotting respectively in 16 benign adrenocortical neoplasms (BANs) and 10 adrenocortical carcinomas (ACCs) along with the adjacent normal adrenal tissues (controls). BCL2/BAX mRNA expression was also analyzed in SW-13 cells after CHCHD2 silencing. MTS, flow cytometry and scratch assays were performed to assess cell viability, apoptosis and invasion respectively. Results BCL2 and CHCHCD2 mRNA and protein expression was increased in BANs compared with normal adrenal tissues whereas BAX was decreased. BAX and CHCHD2 mRNA and protein levels were significantly down-regulated and up-regulated respectively in ACCs compared to either BANs or controls. Expression of the studied genes was not different among cortisol-secreting and non-functional ACAs. No significant association was found between genes’ expression and established prognostic markers of ACCs patients. In-vitro analysis showed that CHCHD2 silencing resulted in reduced cell viability and invasion as well as increased SW-13 cells apoptosis. Conclusions CHCHD2 expression seems to be implicated in adrenal tumourigenesis through BAX/BCL2 pathway similarly to other tumours. However, the exact mechanism needs to be further studied along with the possibility of being a potentional therapeutic target.