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Genotype and allele frequency analysis was performed to study the association between rs12976445 polymorphism and the risk of IA re-bleeding. Western blot, ELISA and real-time RT-PCR were conducted to measure the relative expression of miR-125a, ET1 mRNA and ET1 protein. Computational analysis and luciferase assays were utilized to investigate the association between the expression of miR-125a and ET1 mRNA. No significant differences were observed between IA patients with or without symptoms of re-bleeding. Subsequent analyses indicated that the T allele was significantly associated with the reduced risk of IA re-bleeding. In patients carrying the CC genotype, miR-125a level was up-regulated while ET1 mRNA\/protein levels were reduced compared with those in patients carrying the CT or TT genotype. And ET1 mRNA was identified as a virtual target gene of miR-125a with a potential miR-125a binding site located on its 3\u2019UTR. Accordingly, the ET mRNA\/protein levels could be suppressed by the transfection of miR-125a precursors, but the transfection of ET1 siRNA exhibited no effect on the expression of miR-125a. Therefore, an increased level of miR-125a can lead to the increased risk of IA re-bleeding. Since miR-125a level is higher in CC-genotyped patients, it can be concluded that the presence of T allele in the rs12976445 polymorphism is associated with a lower risk of IA re-bleeding, and miR-125a may be used as a novel diagnostic and therapeutic target for IA rupture.<\/jats:p>","DOI":"10.1038\/s41598-021-04330-4","type":"journal-article","created":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T11:04:34Z","timestamp":1644318274000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Rs12976445 polymorphism is associated with the risk of post-SAH re-bleeding by modulating the expression of microRNA-125 and ET-1"],"prefix":"10.1038","volume":"12","author":[{"given":"Wenping","family":"Xiong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiqi","family":"Yao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zeyuan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,2,8]]},"reference":[{"issue":"5","key":"4330_CR1","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1177\/0271678X20908363","volume":"40","author":"S Marbacher","year":"2020","unstructured":"Marbacher, S., Strange, F., Fr\u00f6s\u00e9n, J. & Fandino, J. 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