Deregulation of microRNA (miRNA) expression in adrenocortical carcinomas has been documented to have diagnostic, prognostic as well as functional implications. Here, we evaluated the mRNA expression of DROSHA, DGCR8, DICER, TARBP2 and PACT, the core components in the miRNA biogenesis pathway, in a cohort of 73 adrenocortical tumors (including 43 adenomas and 30 carcinomas) and 9 normal adrenal cortices using a RT-qPCR approach. Our results show a significant over-expression of TARBP2, DICER and DROSHA in the carcinomas compared to adenomas or adrenal cortices (P<0.001 for all comparisons). Using Western blot and immunohistochemistry analyses, we confirmed the higher expression of TARBP2, DICER and DROSHA at ... More
Deregulation of microRNA (miRNA) expression in adrenocortical carcinomas has been documented to have diagnostic, prognostic as well as functional implications. Here, we evaluated the mRNA expression of DROSHA, DGCR8, DICER, TARBP2 and PACT, the core components in the miRNA biogenesis pathway, in a cohort of 73 adrenocortical tumors (including 43 adenomas and 30 carcinomas) and 9 normal adrenal cortices using a RT-qPCR approach. Our results show a significant over-expression of TARBP2, DICER and DROSHA in the carcinomas compared to adenomas or adrenal cortices (P<0.001 for all comparisons). Using Western blot and immunohistochemistry analyses, we confirmed the higher expression of TARBP2, DICER and DROSHA at the protein level in carcinoma cases. Furthermore, we demonstrate that mRNA expression of TARBP2, but not DICER or DROSHA, is a strong molecular predictor to discriminate between adenomas and carcinomas. Functionally, we showed that inhibition of TARBP2 expression in human NCI-H295R ACC cells resulted in a decreased cell proliferation and induction of apoptosis. TARBP2 over-expression was not related to gene mutations, however copy number gain of the TARBP2 gene was observed in 57% of the carcinomas analyzed. In addition, we identified that miR-195 and miR-497 could directly regulate TARBP2 and DICER expression in ACC cells. This study is the first report demonstrating the deregulation of miRNA processing factors in adrenocortical tumors and showing the clinical and biological impact of TARBP2 over-expression in this tumor type.
