In:
Journal of Cellular and Molecular Medicine, Wiley, Vol. 22, No. 8 ( 2018-08), p. 3808-3815
Abstract:
Interleukin ( IL )‐33/ ST 2 pathway plays crucial roles in tumour growth and metastasis. The aim of this study was to investigate the association of two functional polymorphisms ( IL ‐33 rs7025417 and ST 2 rs3821204) with osteosarcoma ( OS ) risk. The rs7025417 and rs3821204 were genotyped by Taqman assay. IL ‐33 mRNA and protein levels were measured by real‐time PCR or enzyme‐linked immunosorbent assay. The luciferase activity was measured by a dual luciferase reporter gene assay. The allele‐specific transcription factor binding for rs7025417 was examined by Ch IP ‐seq. The IL ‐33 rs7025417 CC genotype was significantly associated with a decreased risk of OS ( CC vs TT : OR = 0.59, 95% CI , 0.41‐0.85; recessive model: OR = 0.68, 95% CI , 0.49‐0.94; C vs T: OR = 0.76, 95% CI , 0.63‐0.91). Combined analysis showed that the IL ‐33 rs7025417 CT / CC ‐ ST 2 rs3821204 CG / CC and the IL ‐33 rs7025417 CT / CC ‐ ST 2 rs3821204 GG genotypes also had a decreased risk of OS . IL ‐33 mRNA and protein levels in OS patients were significantly higher than controls. Patients with the rs7025417 CC genotype exhibited lower levels of IL ‐33 ( P = .03). The rs7025417 C allele presented a lower transcriptional activity by disrupting the binding site to c‐Myb ( P 〈 .01). Moreover, the rs3821204 G/C influences the transcriptional activity and ST 2 mRNA expression by altering the binding site of miR‐202‐3p. These findings suggest that the rs7025417 and rs3821204 may have a combined effect to protect against the development of OS by decreasing the expression levels of IL ‐33 or ST2 .
Type of Medium:
Online Resource
ISSN:
1582-1838
,
1582-4934
DOI:
10.1111/jcmm.2018.22.issue-8
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2076114-4
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