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Updated: Jan 5, 2026

CD Spectroscopy to Study DNA-Protein Interactions
Published on: February 10, 2022
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.
Abstract:
Though primarily a tumor suppressor, TP53 harboring specific missense mutations located in the region encoding the DNA binding domain exhibits a gain of function by transcriptional activation of oncogenes. We performed microarray-based messenger RNA profiling of squamous cell carcinoma of the oral tongue (SCCOT) and identified significant elevation of SMARCD1 in samples exhibiting p53 nuclear stabilization. Activation of SMARCD1 by mutant p53 was confirmed by evaluation of additional tongue cancer samples as well as The Cancer Genome Atlas expression datasets. SMARCD1 knockdown in HNSCC cells resulted in a significant reduction in several tumorigenic characteristics including cell viability, ability to form colonies in liquid and solid media and cell migration. We identified significantly increased SMARCD1 transcript levels in tumor versus matched normal samples in SCCOT as well as in other cancer types. Increased SMARCD1 expression predicted poor survival in HNSCC tumors harboring missense p53 mutations. Our results suggest SMARCD1 to be a novel transcriptional target of mutant p53.
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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