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miRNA失调诱导的胃黏膜相关淋巴组织淋巴瘤:从小鼠到人类

Deregulation of miRNA in -Induced Gastric MALT Lymphoma: From Mice to Human.

作者信息

Blosse Alice, Levy Michael, Robe Cyrielle, Staedel Cathy, Copie-Bergman Christiane, Lehours Philippe

机构信息

INSERM, Université Bordeaux, UMR1053 Bordeaux Research in Translational Oncology, BaRITOn, 33000 Bordeaux, France.

EC2M3: Department of Academic Research (EA7375), Université Paris Est Créteil (UPEC), Val de Marne, 94000 Créteil, France.

出版信息

J Clin Med. 2019 Jun 13;8(6):845. doi: 10.3390/jcm8060845.

Abstract

Gastric MALT lymphoma (GML) is directly caused by infection but occurs only in a small number of infected subjects. Mechanisms underlying the initiation and progression of GML remain unclear. MicroRNAs (miRNAs) are small non-coding RNAs that are now considered as major players in inflammation and carcinogenesis, acting as oncogenes or tumor suppressors. Previous laboratory studies have shown in a GML mouse model that overexpression of a distinct set of five miRNAs (miR-21a, miR-135b, miR-142a, miR-150, miR-155) could play a critical role in the pathogenesis of GML. Our goal was to compare the miRNA expression profile obtained in the GML mouse model to that in human GML (11 cases of GML compared to 17 cases of gastritis control population). RTqPCR on the five dysregulated miRNAs in the GML mouse model and PCR array followed by RTqPCR confirmation showed that four miRNAs were up-regulated (miR-150, miR-155, miR-196a, miR-138) and two miRNAs down-regulated (miR-153, miR-7) in the stomachs of GML patients vs. gastritis control population. The analysis of their validated targets allowed us to postulate that these miRNAs (except miR-138) could act synergistically in a common signaling cascade promoting lymphomagenesis and could be involved in the pathogenesis of GML.

摘要

胃黏膜相关淋巴组织淋巴瘤(GML)由感染直接引起,但仅在少数受感染个体中发生。GML起始和进展的潜在机制仍不清楚。微小RNA(miRNA)是小的非编码RNA,现在被认为是炎症和致癌作用的主要参与者,可作为癌基因或肿瘤抑制因子。先前的实验室研究在GML小鼠模型中表明,一组独特的5种miRNA(miR-21a、miR-135b、miR-142a、miR-150、miR-155)的过表达可能在GML的发病机制中起关键作用。我们的目标是将GML小鼠模型中获得的miRNA表达谱与人类GML中的表达谱进行比较(11例GML与17例胃炎对照人群)。对GML小鼠模型中5种失调的miRNA进行逆转录定量聚合酶链反应(RTqPCR),然后进行PCR阵列分析并经RTqPCR确认,结果显示,与胃炎对照人群相比,GML患者胃中4种miRNA上调(miR-150、miR-155、miR-196a、miR-138),2种miRNA下调(miR-153、miR-7)。对其经过验证的靶标的分析使我们推测,这些miRNA(miR-138除外)可能在促进淋巴瘤发生的共同信号级联反应中协同发挥作用,并可能参与GML的发病机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4913/6616415/2bfed27d9544/jcm-08-00845-g001.jpg

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