This project began with a simple observation. While exploring transcriptional datasets from head and neck squamous cell carcinoma, we noticed that PIAS genes repeatedly appeared among the most dysregulated regulators. Although PIAS proteins are known for their role in SUMOylation and transcriptional control, very little was known about their contribution to this cancer. This gap in the literature sparked the central question of our work: could PIAS genes serve as meaningful biomarkers or therapeutic targets in HNSC?
As we delved deeper, a much more complex picture emerged. Public datasets showed strong up-regulation of PIAS1, PIAS2, PIAS3 and PIAS4, but the mechanisms behind this pattern seemed unclear. We expanded our approach to include promoter methylation, genomic alterations, immune-cell correlations and protein-level validation. The more layers we added, the more consistent the findings became. The evidence pointed toward a coordinated dysregulation of the entire PIAS family.
The experimental phase of the study brought the story to life. When we knocked down PIAS genes, HNSC cells became less invasive, less migratory and less proliferative. Seeing these changes in real time made the computational predictions feel real. This was a turning point in the project and confirmed that PIAS genes are not just biomarkers, but active contributors to tumour behaviour.
The final step, molecular docking, added an unexpected dimension. Identifying potential inhibitors such as Cyclocreatine and Vorinostat opened a new therapeutic angle that we had not initially anticipated. It suggested that PIAS-related vulnerabilities may be pharmaceutically targetable.
This study represents the collective effort to connect genomic signals to biological meaning. By combining multiple databases with bench experiments, we uncovered a clearer view of how PIAS genes contribute to HNSC progression and how they might guide future diagnostic and therapeutic strategies. The journey revealed more than we expected, and we hope it encourages further exploration into this underexamined gene family.