SOX2 suppresses CDKN1A to sustain growth of lung squamous cell carcinoma

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• SOX2 amplification is observed in lung squamous cell carcinoma (lung SCC).
• Identifying consistent SOX2 transcriptional targets in lung SCC has been challenging due to cell line specificity.
• Understanding SOX2 downstream targets is crucial for elucidating lung SCC tumorigenesis.

Purpose of the Study:

• To identify consensus SOX2 downstream genes in lung SCC by analyzing multiple RNA-seq datasets.
• To determine the correlation between SOX2 and its reported target genes in both tumor specimens and cell lines.
• To investigate the functional role of identified SOX2 targets in lung SCC progression.

Main Methods:

• Analyzed RNA-seq data from 178 lung SCC specimens and 105 non-small cell lung cancer (NSCLC) cell lines.
• Correlated SOX2 expression with previously reported SOX2-controlled genes in both datasets.
• Performed biological validation studies, including siRNA experiments, to confirm gene function.

Main Results:

• Identified 15 genes commonly correlated with SOX2 across both lung SCC specimens and NSCLC cell lines.
• Found 4 negatively-correlated genes, including CDKN1A, and 11 positively-correlated genes with SOX2.
• Demonstrated that SOX2 suppresses CDKN1A expression in lung SCC cells, and this suppression mediates SOX2's tumorigenic effect via cell cycle regulation.

Conclusions:

• SOX2 plays a tumorigenic role in lung SCC partially through the suppression of CDKN1A.
• CDKN1A is a key downstream target of SOX2 in lung SCC, impacting cell cycle progression.
• The findings provide insights into the molecular mechanisms of lung SCC driven by SOX2 amplification.