Research Papers:

LSCC SNP variant regulates SOX2 modulation of VDAC3

Jacqueline Chyr, Dongmin Guo and Xiaobo Zhou _

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Oncotarget. 2018; 9:22340-22352. https://doi.org/10.18632/oncotarget.24918

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Jacqueline Chyr1,3, Dongmin Guo2 and Xiaobo Zhou2,3

1Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA

2Center for Bioinformatics and Systems Biology, Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA

3School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA

Correspondence to:

Xiaobo Zhou, email: [email protected]

Keywords: lung cancer; SOX2; eQTL; SNP; topologically associating domain

Received: June 21, 2017     Accepted: February 28, 2018     Published: April 27, 2018


Lung squamous cell carcinoma (LSCC) is a genomically complex malignancy with no effective treatments. Recent studies have found a large number of DNA alterations such as SOX2 amplification in LSCC patients. As a stem cell transcription factor, SOX2 is important for the maintenance of pluripotent cells and may play a role in cancer. To study the downstream mechanisms of SOX2, we employed expression quantitative trait loci (eQTLs) technology to investigate how the presence of SOX2 affects the expression of target genes. We discovered unique eQTLs, such as rs798827-VDAC3 (FDR p-value = 0.0034), that are only found in SOX2-active patients but not in SOX2-inactive patients. SNP rs798827 is within strong linkage disequilibrium (r2 = 1) to rs58163073, where rs58163073 [T] allele increases the binding affinity of SOX2 and allele [TA] decreases it. In our analysis, SOX2 silencing downregulates VDAC3 in two LSCC cell lines. Chromatin conformation capturing data indicates that this SNP is located within the same Topologically Associating Domain (TAD) of VDAC3, further suggesting SOX2’s role in the regulation of VDAC3 through the binding of rs58163073. By first subgrouping patients based on SOX2 activity, we made more relevant eQTL discoveries and our analysis can be applied to other diseases.

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