Functional Genetic Variations at the microRNA Binding-Site in the CD44 Gene Are Associated with Risk of Colorectal Cancer in Chinese Populations
CD44 as one of the most putative stem cell markers plays a key role in many cellular processes, including cancer cell growth and migration. Functional single nucleotide polymorphisms (SNPs) of CD44 may modulate its gene functions and thus cancer risk. In the current study, we investigated if polymor...
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Public Library of Science
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444206/ |
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pubmed-44442062015-06-16 Functional Genetic Variations at the microRNA Binding-Site in the CD44 Gene Are Associated with Risk of Colorectal Cancer in Chinese Populations Wu, Xiao-Min Yang, Hong-Guo Zheng, Bo-An Cao, Hong-Feng Hu, Zhi-Ming Wu, Wei-Ding Research Article CD44 as one of the most putative stem cell markers plays a key role in many cellular processes, including cancer cell growth and migration. Functional single nucleotide polymorphisms (SNPs) of CD44 may modulate its gene functions and thus cancer risk. In the current study, we investigated if polymorphisms in the 3’-untranslated region (UTR) of CD44 are associated with increased susceptibility to colorectal cancer (CRC) by conducting a case-control study of 946 CRC patients and 989 cancer-free controls. Three polymorphisms (rs13347C/T, rs10836347C/T, rs11821102G/A) in the 3’-UTR of CD44 were genotyped. We found that the variant genotypes (CT and TT) of rs13347 (adjusted odds ratio (OR)=1.79, 95% confidence interval (CI)=1.50-2.17) increased an individual’s susceptibility to CRC, compared with rs13347CC homozygous genotypes. We also found that CRC patients with the CT/TT genotype had a 1.6-fold increased risk for developing advanced (stage III + IV) CRC. Furthermore, functional assays showed that the C to T base change at rs13347C/T disrupts the binding site for the microRNA hsa-mir-509-3p, thereby increasing CD44 transcriptional activity and expression level. These findings suggest that the rs13347C/T in microRNA binding site may be potential biomarkers for genetic susceptibility to CRC. Public Library of Science 2015-05-26 /pmc/articles/PMC4444206/ /pubmed/26010608 http://dx.doi.org/10.1371/journal.pone.0127557 Text en © 2015 Wu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Wu, Xiao-Min Yang, Hong-Guo Zheng, Bo-An Cao, Hong-Feng Hu, Zhi-Ming Wu, Wei-Ding |
| spellingShingle |
Wu, Xiao-Min Yang, Hong-Guo Zheng, Bo-An Cao, Hong-Feng Hu, Zhi-Ming Wu, Wei-Ding Functional Genetic Variations at the microRNA Binding-Site in the CD44 Gene Are Associated with Risk of Colorectal Cancer in Chinese Populations |
| author_facet |
Wu, Xiao-Min Yang, Hong-Guo Zheng, Bo-An Cao, Hong-Feng Hu, Zhi-Ming Wu, Wei-Ding |
| author_sort |
Wu, Xiao-Min |
| title |
Functional Genetic Variations at the microRNA Binding-Site in the CD44 Gene Are Associated with Risk of Colorectal Cancer in Chinese Populations |
| title_short |
Functional Genetic Variations at the microRNA Binding-Site in the CD44 Gene Are Associated with Risk of Colorectal Cancer in Chinese Populations |
| title_full |
Functional Genetic Variations at the microRNA Binding-Site in the CD44 Gene Are Associated with Risk of Colorectal Cancer in Chinese Populations |
| title_fullStr |
Functional Genetic Variations at the microRNA Binding-Site in the CD44 Gene Are Associated with Risk of Colorectal Cancer in Chinese Populations |
| title_full_unstemmed |
Functional Genetic Variations at the microRNA Binding-Site in the CD44 Gene Are Associated with Risk of Colorectal Cancer in Chinese Populations |
| title_sort |
functional genetic variations at the microrna binding-site in the cd44 gene are associated with risk of colorectal cancer in chinese populations |
| description |
CD44 as one of the most putative stem cell markers plays a key role in many cellular processes, including cancer cell growth and migration. Functional single nucleotide polymorphisms (SNPs) of CD44 may modulate its gene functions and thus cancer risk. In the current study, we investigated if polymorphisms in the 3’-untranslated region (UTR) of CD44 are associated with increased susceptibility to colorectal cancer (CRC) by conducting a case-control study of 946 CRC patients and 989 cancer-free controls. Three polymorphisms (rs13347C/T, rs10836347C/T, rs11821102G/A) in the 3’-UTR of CD44 were genotyped. We found that the variant genotypes (CT and TT) of rs13347 (adjusted odds ratio (OR)=1.79, 95% confidence interval (CI)=1.50-2.17) increased an individual’s susceptibility to CRC, compared with rs13347CC homozygous genotypes. We also found that CRC patients with the CT/TT genotype had a 1.6-fold increased risk for developing advanced (stage III + IV) CRC. Furthermore, functional assays showed that the C to T base change at rs13347C/T disrupts the binding site for the microRNA hsa-mir-509-3p, thereby increasing CD44 transcriptional activity and expression level. These findings suggest that the rs13347C/T in microRNA binding site may be potential biomarkers for genetic susceptibility to CRC. |
| publisher |
Public Library of Science |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444206/ |
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1613227747409133568 |