LSCC SNP variant regulates SOX2 modulation of VDAC3

Area of Science:

• Genomics
• Cancer Biology
• Molecular Genetics

Background:

• Lung squamous cell carcinoma (LSCC) is a complex cancer lacking effective treatments.
• SOX2, a stem cell transcription factor, is frequently amplified in LSCC and may drive cancer progression.

Purpose of the Study:

• To investigate the downstream gene expression effects of SOX2 in LSCC.
• To identify novel expression quantitative trait loci (eQTLs) associated with SOX2 activity.

Main Methods:

• Employed expression quantitative trait loci (eQTLs) technology to analyze gene expression.
• Utilized SOX2 activity subgrouping for patient analysis.
• Performed SOX2 silencing experiments in LSCC cell lines.
• Analyzed chromatin conformation capture data.

Main Results:

• Discovered unique eQTLs, such as rs798827-VDAC3, specifically in SOX2-active LSCC patients.
• Identified a single nucleotide polymorphism (SNP) rs58163073 influencing SOX2 binding affinity.
• Demonstrated that SOX2 silencing downregulates VDAC3 expression.
• Confirmed the regulatory relationship between SOX2 and VDAC3 via eQTL and chromatin conformation data.

Conclusions:

• SOX2 plays a regulatory role in VDAC3 expression in LSCC.
• Subgrouping patients by SOX2 activity enhances the discovery of relevant eQTLs.
• This methodology can be applied to understand SOX2's role in other diseases.