SMARCD1 is a transcriptional target of specific non-hotspot mutant p53 forms

Raju S R Adduri1,2, Sara A George1,3, Padmavathi Kavadipula1

  • 1Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, India.

Insights

Mutant TP53 protein can activate oncogenes, including SMARCD1, promoting head and neck squamous cell carcinoma (HNSCC) growth and migration. Targeting SMARCD1 may offer a new therapeutic strategy for HNSCC patients with TP53 mutations.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The TP53 tumor suppressor gene, when mutated, can gain oncogenic functions.
  • Specific TP53 missense mutations in the DNA binding domain can lead to transcriptional activation of oncogenes.

Purpose of the Study:

  • To investigate the role of SMARCD1 in head and neck squamous cell carcinoma (HNSCC).
  • To determine if mutant TP53 (p53) activates SMARCD1 expression.
  • To assess the impact of SMARCD1 on HNSCC tumorigenic properties and patient survival.

Main Methods:

  • Microarray-based messenger RNA profiling of oral tongue squamous cell carcinoma (SCCOT).
  • Validation using The Cancer Genome Atlas (TCGA) datasets and additional tongue cancer samples.
  • SMARCD1 knockdown experiments in HNSCC cell lines.
  • Correlation analysis between SMARCD1 expression and patient survival.

Main Results:

  • SMARCD1 was significantly elevated in SCCOT samples with p53 nuclear stabilization.
  • Mutant p53 was confirmed to activate SMARCD1 transcription.
  • SMARCD1 knockdown reduced HNSCC cell viability, colony formation, and migration.
  • Increased SMARCD1 expression correlated with poor survival in HNSCC harboring missense p53 mutations.

Conclusions:

  • SMARCD1 is a novel transcriptional target of mutant p53.
  • Mutant p53-driven SMARCD1 activation contributes to HNSCC progression.
  • SMARCD1 represents a potential therapeutic target in HNSCC with TP53 mutations.

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