Dicer and microRNA expression in multiple sclerosis and response to interferon therapy.
Dicer and microRNA expression in multiple sclerosis and response to interferon therapy.
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DOI：
10.1016/j.jneuroim.2016.01.009
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发表时间：
2016-03-15
影响因子：
3.3
通讯作者：
Tomasi TB
中科院分区：
文献类型：
--
作者：
Magner WJ;Weinstock-Guttman B;Rho M;Hojnacki D;Ghazi R;Ramanathan M;Tomasi TB
在多发性硬化症（MS）中发现了microRNA表达失调；然而，这些变化的机制、它们对治疗的反应以及microRNA变化对MS的影响尚不完全清楚。Dicer介导前体microrna裂解为成熟microrna，并在多种病理中失调。已经证明干扰素在体外调节Dicer，我们假设MS患者的IFNβ1a治疗可能会改变Dicer的表达。在MS患者和健康对照PBL中检测Dicer mRNA和蛋白水平以及microRNA表达。对50例患者对IFNβ1a的急性反应进行了评估。我们发现Dicer蛋白而非mRNA水平在MS患者中下降，而在对IFNβ1a反应良好的患者中，这两种蛋白都是选择性诱导的。描述了复发缓解型多发性硬化症（RRMS）、继发性进展型多发性硬化症（SPMS）和IFNβ1a反应的潜在microRNA生物标志物。患者群体之间Dicer和microRNA表达水平的差异可能有助于了解疾病病程和对IFNβ1a治疗反应的机制。这项工作确定了Dicer调节作为MS病理的潜在介质和治疗靶点。
Dysregulation of microRNA expression has been shown in multiple sclerosis (MS); however, the mechanisms underlying these changes, their response to therapy and the impact of microRNA changes in MS are not completely understood. Dicer mediates the cleavage of precursor microRNAs to mature microRNAs and is dysregulated in multiple pathologies. Having shown that interferons regulate Dicer in vitro, we hypothesized that MS patient IFNβ1a treatment could potentially alter Dicer expression. Dicer mRNA and protein levels, as well as microRNA expression, were determined in MS patient and healthy control PBL. Acute responses to IFNβ1a were assessed in 50 patients. We found that Dicer protein but not mRNA levels decrease in MS patients while both are selectively induced in patients responding well to IFNβ1a. Potential microRNA biomarkers for relapsing remitting multiple sclerosis (RRMS), secondary-progressive multiple sclerosis (SPMS) and IFNβ1a response are described. Contrasts in Dicer and microRNA expression levels between patient populations may offer insight into mechanisms underlying disease courses and responses to IFNβ1a therapy. This work identifies Dicer regulation as both a potential mediator of MS pathology and a therapeutic target.