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外周血miR-372通过直接靶向NLRP12作为溃疡性结肠炎的生物标志物。

Peripheral blood miR-372 as a biomarker for ulcerative colitis via direct targeting of NLRP12.

作者信息

Shen Mengdie, Meng Li'Na

机构信息

Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China.

出版信息

Exp Ther Med. 2019 Aug;18(2):1486-1492. doi: 10.3892/etm.2019.7707. Epub 2019 Jun 25.

Abstract

The present study aimed to investigate the expression pattern and underlying mechanism of microRNA-372 (miR-372) in the progression of ulcerative colitis (UC). Reverse transcription-quantitative polymerase chain reaction was used to measure miR-372 expression levels in the blood and colonic mucosa tissue samples from patients with UC. The present study demonstrated that levels of miR-372 were significantly increased in the blood and colonic mucosa tissue samples from patients with UC compared with healthy controls. Furthermore, the level of serum miR-372 was positively correlated with the level of serum c-reactive protein. Receiver operating characteristic analysis indicated that levels of miR-372 detected in serum and tissue samples could be used to screen for patients with UC from healthy controls. These results indicated a potential role of miR-372 as a diagnostic marker and therapeutic target for patients with UC. Furthermore, a conserved miR-372 binding site in the 3'untranslated region of the NLR family pyrin domain containing 12 (NLRP12) was identified. Dual luciferase assay demonstrated that overexpression of miR-372 significantly reduced the relative luciferase activity of pmirGLO-NLRP12-3'UTR compared with control pmirGLO. In addition, western blot analysis indicated that overexpression of miR-372 significantly decreased the protein expression level of NLRP12. Therefore it was hypothesized that miR-372 may promote the progression of UC by suppressing NLRP12 protein expression and thereby inducing the excessive production of inflammatory cytokines. In conclusion, high levels of miR-372 detected in peripheral blood samples may serve a role as a potential biomarker to screen potential patients with UC from healthy controls.

摘要

本研究旨在探讨微小RNA-372(miR-372)在溃疡性结肠炎(UC)进展中的表达模式及潜在机制。采用逆转录-定量聚合酶链反应检测UC患者血液和结肠黏膜组织样本中miR-372的表达水平。本研究表明,与健康对照相比,UC患者血液和结肠黏膜组织样本中miR-372水平显著升高。此外,血清miR-372水平与血清C反应蛋白水平呈正相关。受试者工作特征分析表明,血清和组织样本中检测到的miR-372水平可用于从健康对照中筛选UC患者。这些结果表明miR-372作为UC患者诊断标志物和治疗靶点的潜在作用。此外,在含NLR家族pyrin结构域12(NLRP12)的3'非翻译区鉴定出一个保守的miR-372结合位点。双荧光素酶测定表明,与对照pmirGLO相比,miR-372过表达显著降低了pmirGLO-NLRP12-3'UTR的相对荧光素酶活性。此外,蛋白质印迹分析表明,miR-372过表达显著降低了NLRP12的蛋白表达水平。因此,推测miR-372可能通过抑制NLRP12蛋白表达从而诱导炎性细胞因子过度产生来促进UC的进展。总之,在外周血样本中检测到的高水平miR-372可能作为一种潜在生物标志物,用于从健康对照中筛选潜在的UC患者。

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