Knockdown of SF-1 and RNF31 affects components of steroidogenesis, TGFβ, and Wnt/β-catenin signaling in adrenocortical carcinoma cells.
2012 (English)In: PloS one, ISSN 1932-6203, Vol. 7, no 3, e32080- p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2012. Vol. 7, no 3, e32080- p.
Cell and Molecular Biology
Research subject SRA - Molecular Bioscience
IdentifiersURN: urn:nbn:se:kth:diva-165359DOI: 10.1371/journal.pone.0032080ISI: 000303062800012PubMedID: 22427816ScopusID: 2-s2.0-84857929663OAI: oai:DiVA.org:kth-165359DiVA: diva2:808121
FunderSwedish Cancer SocietySwedish Research Council
QC 201505052015-04-272015-04-272015-05-05Bibliographically approved