Knockdown of SF-1 and RNF31 affects components of steroidogenesis, TGFβ, and Wnt/β-catenin signaling in adrenocortical carcinoma cells - Abstract

The orphan nuclear receptor Steroidogenic Factor-1 (SF-1, NR5A1) is a critical regulator of development and homeostasis of the adrenal cortex and gonads.

We recently showed that a complex containing E3 ubiquitin ligase RNF31 and the known SF-1 corepressor DAX-1 (NR0B1) interacts with SF-1 on target promoters and represses transcription of steroidogenic acute regulatory protein (StAR) and aromatase (CYP19) genes. To further evaluate the role of SF-1 in the adrenal cortex and the involvement of RNF31 in SF-1-dependent pathways, we performed genome-wide gene-expression analysis of adrenocortical NCI-H295R cells where SF-1 or RNF31 had been knocked down using RNA interference. We find RNF31 to be deeply connected to cholesterol metabolism and steroid hormone synthesis, strengthening its role as an SF-1 coregulator. We also find intriguing evidence of negative crosstalk between SF-1 and both transforming growth factor (TGF) β and Wnt/β-catenin signaling. This crosstalk could be of importance for adrenogonadal development, maintenance of adrenocortical progenitor cells and the development of adrenocortical carcinoma. Finally, the SF-1 gene profile can be used to distinguish malignant from benign adrenocortical tumors, a finding that implicates SF-1 in the development of malignant adrenocortical carcinoma.

Written by:
Ehrlund A, Jonsson P, Vedin LL, Williams C, Gustafsson JÅ, Treuter E.   Are you the author?
Center for Biosciences, Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.

Reference: PLoS One. 2012;7(3):e32080.
doi: 10.1371/journal.pone.0032080


PubMed Abstract
PMID: 22427816

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