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A functional variant at the miRNA binding site in HMGB1 gene is associated with risk of oral squamous cell carcinoma
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 imp...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5470997/ https://www.ncbi.nlm.nih.gov/pubmed/28423715 http://dx.doi.org/10.18632/oncotarget.16120 |
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author | Lin, Chiao-Wen Chou, Ying-Erh Yeh, Chia-Ming Yang, Shun-Fa Chuang, Chun-Yi Liu, Yu-Fan |
author_facet | Lin, Chiao-Wen Chou, Ying-Erh Yeh, Chia-Ming Yang, Shun-Fa Chuang, Chun-Yi Liu, Yu-Fan |
author_sort | Lin, Chiao-Wen |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5470997 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-54709972017-06-27 A functional variant at the miRNA binding site in HMGB1 gene is associated with risk of oral squamous cell carcinoma Lin, Chiao-Wen Chou, Ying-Erh Yeh, Chia-Ming Yang, Shun-Fa Chuang, Chun-Yi Liu, Yu-Fan Oncotarget Research Paper 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. Impact Journals LLC 2017-03-11 /pmc/articles/PMC5470997/ /pubmed/28423715 http://dx.doi.org/10.18632/oncotarget.16120 Text en Copyright: © 2017 Lin et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Lin, Chiao-Wen Chou, Ying-Erh Yeh, Chia-Ming Yang, Shun-Fa Chuang, Chun-Yi Liu, Yu-Fan A functional variant at the miRNA binding site in HMGB1 gene is associated with risk of oral squamous cell carcinoma |
title | A functional variant at the miRNA binding site in HMGB1 gene is associated with risk of oral squamous cell carcinoma |
title_full | A functional variant at the miRNA binding site in HMGB1 gene is associated with risk of oral squamous cell carcinoma |
title_fullStr | A functional variant at the miRNA binding site in HMGB1 gene is associated with risk of oral squamous cell carcinoma |
title_full_unstemmed | A functional variant at the miRNA binding site in HMGB1 gene is associated with risk of oral squamous cell carcinoma |
title_short | A functional variant at the miRNA binding site in HMGB1 gene is associated with risk of oral squamous cell carcinoma |
title_sort | functional variant at the mirna binding site in hmgb1 gene is associated with risk of oral squamous cell carcinoma |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5470997/ https://www.ncbi.nlm.nih.gov/pubmed/28423715 http://dx.doi.org/10.18632/oncotarget.16120 |
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