Reconciling the Regulatory Targets of SF-1/NR5A1 in Adrenocortical Carcinoma
Three independent groups performed closely related SF-1 perturbation experiments in the same H295R cell model and obtained apparently divergent target-gene lists. The discrepancy was explicitly discussed in a 2015 review and remained unresolved for more than a decade.
Our 2025 study reanalyzed the original datasets under a unified analytical framework and used an independently inferred NR5A1 regulon — reconstructed in our 2022 regulatory-network study — as an external reference. The analysis demonstrated convergence across the perturbation phenotypes despite the limited overlap among the originally reported genes.
We developed a threshold-optimization approach to recover consensus gene sets, and showed experimentally that SF-1 dosage and exposure time contribute to heterogeneous target-gene responses. The study also demonstrated negative autoregulation of the endogenous SF-1 transcript.
Reconstruction of the adrenocortical carcinoma regulatory network that produced the NR5A1 regulon later used as the external reference. Figure 1 of Muzzi et al., Cancers 2022 (CC BY 4.0).
A review explicitly discusses the divergence between the published SF-1 target-gene lists.
Our regulatory-network study infers the NR5A1 regulon later used as an external reference.
Abstract Award for Outstanding Contribution at the 9th International Adrenal Cancer Symposium, MD Anderson Cancer Center.
The reconciliation study is published in the European Journal of Endocrinology.
My contribution: I conceived and executed the integrative strategy, developed the threshold-optimization approach, introduced a methodological adjustment for a specific analytical limitation, performed the full analysis and interpretation, and led the manuscript writing. The work was developed with the Institut de Pharmacologie Moléculaire et Cellulaire in France.
Recognition
Abstract Award for Outstanding Contribution
9th International Adrenal Cancer Symposium
MD Anderson Cancer Center — 2024
- View award certificate ↗
- Institutional feature ↗ Pelé Pequeno Príncipe Research Institute
Publications & sources
- 2025 study — European Journal of Endocrinology ↗ DOI: 10.1093/ejendo/lvaf138
- 2022 NR5A1 regulatory-network paper ↗ Cancers · DOI: 10.3390/cancers14215279
- 2015 review ↗ Where the discrepancy was discussed