PMID- 29854282
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240326
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 9
IP  - 32
DP  - 2018 Apr 27
TI  - LSCC SNP variant regulates SOX2 modulation of VDAC3.
PG  - 22340-22352
LID - 10.18632/oncotarget.24918 [doi]
AB  - 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 (r(2) = 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.
FAU - Chyr, Jacqueline
AU  - Chyr J
AD  - Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 
      27157, USA.
AD  - School of Biomedical Informatics, University of Texas Health Science Center at 
      Houston, Houston, TX 77030, USA.
FAU - Guo, Dongmin
AU  - Guo D
AD  - Center for Bioinformatics and Systems Biology, Department of Radiology, Wake 
      Forest School of Medicine, Winston-Salem, NC 27157, USA.
FAU - Zhou, Xiaobo
AU  - Zhou X
AD  - Center for Bioinformatics and Systems Biology, Department of Radiology, Wake 
      Forest School of Medicine, Winston-Salem, NC 27157, USA.
AD  - School of Biomedical Informatics, University of Texas Health Science Center at 
      Houston, Houston, TX 77030, USA.
LA  - eng
GR  - R01 GM123037/GM/NIGMS NIH HHS/United States
GR  - U01 AR069395/AR/NIAMS NIH HHS/United States
GR  - U01 CA166886/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20180427
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5976468
OTO - NOTNLM
OT  - SNP
OT  - SOX2
OT  - eQTL
OT  - lung cancer
OT  - topologically associating domain
COIS- CONFLICTS OF INTEREST The authors declare no conflicts of interest.
EDAT- 2018/06/02 06:00
MHDA- 2018/06/02 06:01
PMCR- 2018/04/27
CRDT- 2018/06/02 06:00
PHST- 2017/06/21 00:00 [received]
PHST- 2018/02/28 00:00 [accepted]
PHST- 2018/06/02 06:00 [entrez]
PHST- 2018/06/02 06:00 [pubmed]
PHST- 2018/06/02 06:01 [medline]
PHST- 2018/04/27 00:00 [pmc-release]
AID - 24918 [pii]
AID - 10.18632/oncotarget.24918 [doi]
PST - epublish
SO  - Oncotarget. 2018 Apr 27;9(32):22340-22352. doi: 10.18632/oncotarget.24918. 
      eCollection 2018 Apr 27.