MicroRNA expression changes during interferon-beta treatment in the peripheral blood of multiple sclerosis patients.
MicroRNA expression changes during interferon-beta treatment in the peripheral blood of multiple sclerosis patients.
复制标题
多发性硬化症患者外周血中的干扰素β治疗过程中的microRNA表达变化。
DOI：
10.3390/ijms140816087
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发表时间：
2013-08-05
影响因子：
5.6
通讯作者：
Zettl UK
中科院分区：
文献类型：
--
作者：
Hecker M;Thamilarasan M;Koczan D;Schröder I;Flechtner K;Freiesleben S;Füllen G;Thiesen HJ;Zettl UK
MicroRNAs(MiRNAs)是一种非编码的小RNA分子，充当基因表达的转录后调节因子。它们参与了许多生物学过程，它们的失调与包括多发性硬化症(MS)在内的各种疾病有关。干扰素-β被广泛用于多发性硬化患者的一线免疫调节治疗。在这里，我们提出了第一个纵向研究的miRNA表达的变化，以响应干扰素-β治疗。分别于治疗前、治疗后2天、4天、1个月采集临床隔离综合征(CIS)和复发缓解期MS(RRMS)患者的外周血单个核细胞(PBMC)。我们使用实时定量PCR阵列和Affymetrix微阵列并行地测量了651个成熟miRNAs和大约19,000个mRNAs的表达。我们观察到，干扰素-β反应基因的上调伴随着几个miRNAs的下调，包括mir-29家族的成员。这些差异表达的miRNAs被发现与细胞凋亡过程和干扰素反馈环有关。通过整合来自不同数据库的信息，构建了miRNA-mRNA靶向相互作用网络。我们的结果表明，miRNA介导的调节在干扰素-β的作用机制中发挥着重要作用，不仅在MS的治疗中，而且在正常的免疫反应中也是如此。血液中miRNA的表达水平可以作为干扰素-β治疗生物学效应的生物标记物，可以预测个体疾病的活动和进展。
MicroRNAs (miRNAs) are small non-coding RNA molecules acting as post-transcriptional regulators of gene expression. They are involved in many biological processes, and their dysregulation is implicated in various diseases, including multiple sclerosis (MS). Interferon-beta (IFN-beta) is widely used as a first-line immunomodulatory treatment of MS patients. Here, we present the first longitudinal study on the miRNA expression changes in response to IFN-beta therapy. Peripheral blood mononuclear cells (PBMC) were obtained before treatment initiation as well as after two days, four days, and one month, from patients with clinically isolated syndrome (CIS) and patients with relapsing-remitting MS (RRMS). We measured the expression of 651 mature miRNAs and about 19,000 mRNAs in parallel using real-time PCR arrays and Affymetrix microarrays. We observed that the up-regulation of IFN-beta-responsive genes is accompanied by a down-regulation of several miRNAs, including members of the mir-29 family. These differentially expressed miRNAs were found to be associated with apoptotic processes and IFN feedback loops. A network of miRNA-mRNA target interactions was constructed by integrating the information from different databases. Our results suggest that miRNA-mediated regulation plays an important role in the mechanisms of action of IFN-beta, not only in the treatment of MS but also in normal immune responses. miRNA expression levels in the blood may serve as a biomarker of the biological effects of IFN-beta therapy that may predict individual disease activity and progression.
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影响因子：
3.3
作者：
Guerau-de-Arellano, Mireia;Alder, Hansjuerg;Ozer, Hatice Gulcin;Lovett-Racke, Amy;Racke, Michael K.
通讯作者：
Racke, Michael K.
影响因子：
64.8
作者：
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通讯作者：
Nagar B
影响因子：
30.8
作者：
Bentwich, I;Avniel, A;Bentwich, Z
通讯作者：
Bentwich, Z
影响因子：
2.2
作者：
Cetrulo Lorenzi, Julio Cesar;Brum, Doralina G.;Silva, Wilson Araujo, Jr.
通讯作者：
Silva, Wilson Araujo, Jr.
影响因子：
2.1
作者：
Goertsches, Robert H.;Hecker, Michael;Zettl, Uwe K.
通讯作者：
Zettl, Uwe K.