Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 23, Issue 9, Pages 6173-6181Publisher
WILEY
DOI: 10.1111/jcmm.14499
Keywords
ischaemic stroke; luciferase activity; polymorphism; taurine-upregulated gene 1; transcriptional factor
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Funding
- National Natural Science Foundation of China [81560552]
- Natural Science Foundation of Guangxi, China [2018GXNSFAA138120]
- Key Research Projects of Guangxi, China [2018AB58018]
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Taurine-upregulated gene 1 (TUG1), a kind of long non-coding RNAs (lncRNAs), was up-regulated in ischaemic stroke (IS) with the function of promoting neuron apoptosis. In this study, we aimed to investigate the association of TUG1 polymorphisms with IS risk. The TUG1 polymorphisms were genotyped using a custom-by-design 48-Plex SNPscan kit. The promoter activity was measured using the dual luciferase reporter assay. Relative expression of TUG1 in IS patients was analysed using quantitative PCR and the binding of TUG1 rs2240183 polymorphism to transcription factor was analysed using chromatin immunoprecipitation (ChlP) assay. The rs2240183 CT/CC genotypes and C allele in the promoter of TUG1 were associated with an increased risk of IS (CT/CC vs. TT: adjusted OR = 1.70, 95% CI, 1.16-2.49, P = 0.006; C vs. T: adjusted OR =1.47, 95% CI, 1.12-1.93, P = 0.005). Logistic regression analysis showed that the rs2240183 was a risk factor of IS besides TC, TG, HDL-C, LDL-C, VLDL-C, Apo-Al, Apo-B and NEFA. Further functional analysis revealed that the TUG1 rs2240183 C allele exhibited higher transcriptional activity and TUG1 expression levels (P < 0.01). The ChIP assay showed that the rs2240183 C allele binds to transcriptional factor GATA-1. These findings indicate that the rs2240183 C allele was associated with a higher risk of IS possibly by binding to GATA-1 and elevating TUG1 levels.
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