Oncotarget

Research Papers:

A functional variant at the miRNA binding site in HMGB1 gene is associated with risk of oral squamous cell carcinoma

Chiao-Wen Lin, Ying-Erh Chou, Chia-Ming Yeh, Shun-Fa Yang, Chun-Yi Chuang and Yu-Fan Liu _

PDF  |  HTML  |  How to cite

Oncotarget. 2017; 8:34630-34642. https://doi.org/10.18632/oncotarget.16120

Metrics: PDF 1644 views  |   HTML 2880 views  |   ?  


Abstract

Chiao-Wen Lin1,2, Ying-Erh Chou3,4, Chia-Ming Yeh4,5, Shun-Fa Yang4,5, Chun-Yi Chuang3,6 and Yu-Fan Liu7,8

1Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan

2Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan

3School of Medicine, Chung Shan Medical University, Taichung, Taiwan

4Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan

5Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan

6Department of Otolaryngology, Chung Shan Medical University Hospital, Taichung, Taiwan

7Department of Biomedical Sciences, College of Medicine Sciences and Technology, Chung Shan Medical University, Taichung, Taiwan

8Division of Allergy, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan

Correspondence to:

Yu-Fan Liu, email: [email protected]

Keywords: HMGB1, polymorphism, OSCC, bioinformatics analysis, haplotypes

Received: January 04, 2017    Accepted: February 15, 2017    Published: March 11, 2017

ABSTRACT

Oral squamous cell carcinoma (OSCC) is a common malignancy that has been causally associated with both hereditary and acquired factors. The high mobility group box 1 (HMGB1) gene plays an important role as a DNA chaperone to help maintain nuclear homeostasis. Altered expression of HMGB1 has been implicated in a wide range of pathological processes, including inflammation and cancer. The present study explores the impact of HMGB1 gene polymorphisms, combined with environmental risks regarding susceptibility to oral tumorigenesis. Four single-nucleotide polymorphisms (SNPs) of the HMGB1 gene, rs1412125, rs2249825, rs1045411, and rs1360485, were evaluated in 1,200 normal controls and 772 patients with OSCC. We found an association between the wild-type allele of rs1045411 and genotypes CT and CT/TT (AOR=0.754, 95% CI=0.582-0.978 and AOR=0.778, 95% CI=0.609-0.995, respectively). Additionally, bioinformatics analysis was used to characterize the functional relevance of these variants for the miRNA-505-5p binding site and transcriptional regulation by the HMGB1 3’-UTR and promoter regions. Moreover, in considering behavioral exposure to environmental carcinogens, the presence of the four HMGB1 SNPs, combined with/without betel quid chewing and smoking showed, profoundly synergistic effects on the risk of OSCC. In conclusion, we present a potential clinical relevance for HMGB1 variants in OSCC, as well as associations between HMGB1 polymorphisms, haplotypes and environmental risk factors. The finding may help in development of optimal therapeutic approaches for OSCC patients.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 16120