Two polymorphisms of CD44 3’UTR weaken the binding of miRNAs and associate with naso-pharyngeal carcinoma in a Chinese population

F. Lou, H.-N. Ma, L. Xu, M. Chen, Y.-B. Zhu

Department of Otolaryngology of The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, China. drzybzj@163.com

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• Oncology

OBJECTIVE: CD44 is a member of adhesion molecule families whose function is closely associated with cancer cell metastatic spread and drug resistance. CD44 is expressed as a wide variety of isoforms but 3’ untranslated region (3’UTR) is conserved relatively and it is confirmed that more than ten miRNAs regulate the expression of CD44. The aim of this paper is to investigate the association between polymorphisms existed in CD44 3’UTR and nasopharyngeal carcinoma (NPC).

PATIENTS AND METHODS: We scanned 1.5kb of CD44 3’UTR in a 287 patients and 507 controls Chinese Han population. After statistical analysis we found that the minor alleles of rs13347 C/T and rs115214213 T/C are associated with NPC (OR = 1.94 95% CI = 1.44-2.62; OR = 2.07 95% CI = 1.65-2.60). By using bioinformatics tools, we found that rs115214213 may exist in the target region of miR-590-3p. Subsequently, we confirmed that miR-590-3p can repress CD44 expression and promote the apoptosis of CNE2 cells induced by cisplatin in vitro. After that, our transient transfection focusing on reporter gene expression modulated by CD44 3’UTR demonstrated that the presence of an rs13347T allele and rs115214213C allele led to greater transcriptional activity than the rs13347C allele and rs115214213T allele. Similarly, more CD44 expression was shown in minor allele carriers in our western blotting results.

CONCLUSIONS: All these findings suggest that CD44 rs13347C>T and rs115214213T>C polymorphisms may affect NPC development by improving CD44 expression.

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