Ferraresi et al. 2025.
This work represents part of my Master thesis research conducted in the lab of Prof. Isidoro.
Hypothesis
Starting from our previous observations implicating NKX3‑2—a transcriptional repressor of the NK family—as a potential regulator of ovarian cancer (OC) progression, we further assessed its prognostic significance across publicly available cancer patient datasets.
Moreover we decided to study the possible interaction of NKX3-2 with P53 based on previous transcriptomic data from the lab showing their negative correlation.
Main findings
- High NKX3-2 expression correlates with poorer outcomes
- Across multiple solid tumor datasets (including ovarian cancer), elevated NKX3‑2 expression was linked to shorter overall survival
- In TCGA ovarian cancer samples, NKX3‑2 mRNA inversely correlated with TP53; cases with high NKX3‑2/low TP53 showed worse prognosis, whereas low NKX3‑2/high TP53 indicated better survival.
- P53 represses NKX3-2 at protein levels, but not at the transcript levels, by driving its autophagic degradation
- In ovarian cancer cell lines with varied TP53 status, p53 overexpression led to decreased NKX3‑2 protein, while p53 knockdown increased it. NKX3‑2 manipulation didn’t affect p53 levels, and NKX3‑2 mRNA remained unchanged—suggesting post-transcriptional regulation
- NKX3-2 – Autophagy signature correlates with predictive prognosis in OC patients
- In ovarian cancer patients with low NKX3‑2 and high MAP1LC3B (a marker of active autophagy) had significantly better survival
Take-home message
We demonstrate that p53 binds NKX3‑2 and directs its selective degradation via autophagy, unveiling a novel regulatory axis in ovarian cancer.
Since NKX3‑2 acts as a negative prognostic marker—and its suppression via autophagy correlates with improved outcomes—the NKX3‑2/autophagy signature could serve as a powerful tool for patient stratification and personalized therapeutic strategies.
Link to the original article: https://www.mdpi.com/2073-4409/14/11/765