期刊
FEBS LETTERS
卷 589, 期 16, 页码 2087-2093出版社
WILEY
DOI: 10.1016/j.febslet.2015.06.029
关键词
Activating transcription factor 1; Essential hypertension; microRNA-1283; Single nucleotide polymorphism; Association study
资金
- National Nature Science Foundation of China [81270315]
- Provincial Financial Department of Jilin, China [2012006]
- Science and Technology Department of Changchun, China [14KG063]
Activating transcription factor 1 (ATF1) may be involved in essential hypertension (EH) by induction of NADPH oxidase 1 (NOX1) and radical oxygen species (ROSS) production. Abnormal expression of ATF1 was found in EH in previous microarray analysis. Here we tested whether a single nucleotide polymorphism (SNP) located in the 3'-untranslated region (3'UTR) of ATF1 was associated with EH susceptibility by affecting microRNA (miRNA) binding. In silico analysis indicated that rs11169571 (T>C) was a candidate SNP to modulate miRNA: ATF1 mRNA complex, with the greatest changed energy for hsa-miR-1283, and the luciferase reporter analysis showed that miR-1283 inhibited the activity of the reporter vector carrying -T allele, but not the -C allele. In addition, inhibition of miR-1283 in HA-VSMCs enhanced the expression of ATF1 mRNA as well as the ROS levels. Further case-control study showed that rs11169571 was significantly associated with increased risk of EH. Finally, we observed an increased ATF1 protein level in peripheral blood of EH patients with CC carriers compared to IT carriers of rs11169571, with an intermediate ATF1 level in TC carriers. These results suggested that rs11169571 of ATF1 gene may be associated with EH, and the SNP-modified posttranscriptional gene regulation by miRNAs could be a potentially pathogenetic mechanism of EH. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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