Functional Genetic Variations at the MicroRNA Binding-Site in the CD44 Gene Are Associated with Risk of Colorectal Cancer in Chinese Populations

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2015 May 27

PMID 26010608

Citations 15

Authors

Xiao-Min Wu

Hong-Guo Yang

Bo-An Zheng

Hong-Feng Cao

Zhi-Ming Hu

Wei-Ding Wu

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

CD44 rs13347C>T Variants in 3'UTR and Prostate Neoplasms: A Case-control Study and Bioinformatics Approach.

Moudi E, Heydari M, Hosseinzadeh Colagar A Int J Mol Cell Med. 2024; 12(3):275-287.

PMID: 38751654 PMC: 11092902. DOI: 10.22088/IJMCM.BUMS.12.3.275.

SNP-Target Genes Interaction Perturbing the Cancer Risk in the Post-GWAS.

Yang W, Zhang T, Song X, Dong G, Xu L, Jiang F Cancers (Basel). 2022; 14(22).

PMID: 36428729 PMC: 9688512. DOI: 10.3390/cancers14225636.

The Importance of SNPs at miRNA Binding Sites as Biomarkers of Gastric and Colorectal Cancers: A Systematic Review.

Hajibabaie F, Abedpoor N, Assareh N, Tabatabaiefar M, Shariati L, Zarrabi A J Pers Med. 2022; 12(3).

PMID: 35330456 PMC: 8954022. DOI: 10.3390/jpm12030456.

The rs13347 Polymorphism of the CD44 Gene Is Associated with the Risk of Kidney Stones Disease in the Chinese Han Population of Northeast Sichuan, China.

Ying Q, Liu G, Zhou W, Lan J, Du J, Tang X Comput Math Methods Med. 2022; 2022:6481260.

PMID: 35069788 PMC: 8776438. DOI: 10.1155/2022/6481260.

Construction of circRNA-based ceRNA network and its prognosis-associated subnet of clear cell renal cell carcinoma.

Zhang Y, Zhang Y, Feng Y, Zhang N, Chen S, Gu C Cancer Med. 2021; 10(22):8210-8221.

PMID: 34569727 PMC: 8607260. DOI: 10.1002/cam4.4311.

References

Gerger A, Zhang W, Yang D, Bohanes P, Ning Y, Winder T . Common cancer stem cell gene variants predict colon cancer recurrence. Clin Cancer Res. 2011; 17(21):6934-43. DOI: 10.1158/1078-0432.CCR-11-1180. View

Goodison S, Urquidi V, Tarin D . CD44 cell adhesion molecules. Mol Pathol. 2000; 52(4):189-96. PMC: 395698. DOI: 10.1136/mp.52.4.189. View

Dalerba P, Dylla S, Park I, Liu R, Wang X, Cho R . Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci U S A. 2007; 104(24):10158-63. PMC: 1891215. DOI: 10.1073/pnas.0703478104. View

Zheng J, Jiang L, Zhang L, Yang L, Deng J, You Y . Functional genetic variations in the IL-23 receptor gene are associated with risk of breast, lung and nasopharyngeal cancer in Chinese populations. Carcinogenesis. 2012; 33(12):2409-16. DOI: 10.1093/carcin/bgs307. View

Yang L, Parkin D, Li L, Chen Y . Time trends in cancer mortality in China: 1987-1999. Int J Cancer. 2003; 106(5):771-83. DOI: 10.1002/ijc.11300. View

Seth A, Gote L, Nagarkatti M, Nagarkatti P . T-cell-receptor-independent activation of cytolytic activity of cytotoxic T lymphocytes mediated through CD44 and gp90MEL-14. Proc Natl Acad Sci U S A. 1991; 88(17):7877-81. PMC: 52407. DOI: 10.1073/pnas.88.17.7877. View

Song M, Gong J, Giovannucci E, Berndt S, Brenner H, Chang-Claude J . Genetic variants of adiponectin and risk of colorectal cancer. Int J Cancer. 2014; 137(1):154-64. PMC: 4405454. DOI: 10.1002/ijc.29360. View

Screaton G, Bell M, Jackson D, Cornelis F, Gerth U, Bell J . Genomic structure of DNA encoding the lymphocyte homing receptor CD44 reveals at least 12 alternatively spliced exons. Proc Natl Acad Sci U S A. 1992; 89(24):12160-4. PMC: 50718. DOI: 10.1073/pnas.89.24.12160. View

Li N, Zheng J, Li H, Deng J, Hu M, Wu H . Identification of chimeric TSNAX-DISC1 resulting from intergenic splicing in endometrial carcinoma through high-throughput RNA sequencing. Carcinogenesis. 2014; 35(12):2687-97. DOI: 10.1093/carcin/bgu201. View

10.

Winder T, Ning Y, Yang D, Zhang W, Power D, Bohanes P . Germline polymorphisms in genes involved in the CD44 signaling pathway are associated with clinical outcome in localized gastric adenocarcinoma. Int J Cancer. 2010; 129(5):1096-104. PMC: 3139396. DOI: 10.1002/ijc.25787. View

11.

Udabage L, Brownlee G, Nilsson S, Brown T . The over-expression of HAS2, Hyal-2 and CD44 is implicated in the invasiveness of breast cancer. Exp Cell Res. 2005; 310(1):205-17. DOI: 10.1016/j.yexcr.2005.07.026. View

12.

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun M . Cancer statistics, 2009. CA Cancer J Clin. 2009; 59(4):225-49. DOI: 10.3322/caac.20006. View

13.

Jiang L, Deng J, Zhu X, Zheng J, You Y, Li N . CD44 rs13347 C>T polymorphism predicts breast cancer risk and prognosis in Chinese populations. Breast Cancer Res. 2012; 14(4):R105. PMC: 3680922. DOI: 10.1186/bcr3225. View

14.

Huxley R, Ansary-Moghaddam A, Clifton P, Czernichow S, Parr C, Woodward M . The impact of dietary and lifestyle risk factors on risk of colorectal cancer: a quantitative overview of the epidemiological evidence. Int J Cancer. 2009; 125(1):171-80. DOI: 10.1002/ijc.24343. View

15.

OBrien C, Pollett A, Gallinger S, Dick J . A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2006; 445(7123):106-10. DOI: 10.1038/nature05372. View

16.

Li W, Zheng J, Deng J, You Y, Wu H, Li N . Increased levels of the long intergenic non-protein coding RNA POU3F3 promote DNA methylation in esophageal squamous cell carcinoma cells. Gastroenterology. 2014; 146(7):1714-26.e5. DOI: 10.1053/j.gastro.2014.03.002. View

17.

Du L, Wang H, He L, Zhang J, Ni B, Wang X . CD44 is of functional importance for colorectal cancer stem cells. Clin Cancer Res. 2008; 14(21):6751-60. DOI: 10.1158/1078-0432.CCR-08-1034. View

18.

Tsong W, Koh W, Yuan J, Wang R, Sun C, Yu M . Cigarettes and alcohol in relation to colorectal cancer: the Singapore Chinese Health Study. Br J Cancer. 2007; 96(5):821-7. PMC: 2360085. DOI: 10.1038/sj.bjc.6603623. View

19.

Zhai Q, Zhou L, Zhao C, Wan J, Yu Z, Guo X . Identification of miR-508-3p and miR-509-3p that are associated with cell invasion and migration and involved in the apoptosis of renal cell carcinoma. Biochem Biophys Res Commun. 2012; 419(4):621-6. DOI: 10.1016/j.bbrc.2012.02.060. View

20.

Rafi A, Nagarkatti M, Nagarkatti P . Hyaluronate-CD44 interactions can induce murine B-cell activation. Blood. 1997; 89(8):2901-8. View