Morphine and microRNA Activity: Is There a Relation with Addiction?
Morphine and microRNA Activity: Is There a Relation with Addiction?
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DOI：
10.3389/fgene.2012.00223
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发表时间：
2012
影响因子：
3.7
通讯作者：
Rodríguez RE
中科院分区：
文献类型：
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作者：
Rodríguez RE
当我们谈论吸毒成瘾时，我们实际上是在处理一个极其复杂的系统，其中仍然存在许多未知数，仍然存在许多空白或缺失环节。最近的研究已经确定了几种特定miRNA的表达谱的变化，这些变化影响这些分子与其在各种疾病（包括成瘾）中的靶标之间的相互作用，并且可以作为更有效治疗的有价值的靶标。在这篇综述中，我们总结的结果清楚地表明，几个吗啡相关的miRNAs在定义成瘾的机制中发挥作用。在这方面，吗啡已显示在不同miRNA的调节中具有重要作用，如miR-let-7 [其作为μ阿片受体（莫尔）mRNA移动到P体中的介体起作用，导致翻译抑制]、miR-23 b（参与在转录后水平连接莫尔表达和吗啡处理），和miR-190（神经源性分化的关键转录后阻遏物，NeuroD）。芬太尼通过减少miR-190的量来增加NeuroD的水平，但吗啡不影响NeuroD的水平。我们还讨论了吗啡，miRNAs和免疫系统之间的关系，基于发现吗啡治疗单核细胞导致几种抗HIV miRNAs（mir-28，125 b，150和382）的减少。本文综述了miR-133 b及其通过吗啡作用参与成瘾的可能性。我们通过总结miR-133 b在不同病理过程，特别是癌症中的活性，确定了miR-133 b作为调节因子的重要性。使用斑马鱼作为研究模型，我们讨论了mir-133 b，多巴胺能系统和吗啡之间的关系，考虑：（1）吗啡调节miR-133 b及其靶转录物Pitx 3的表达，（2）斑马鱼μ阿片受体（zfMOR）在吗啡诱导的miR-133 b调节中的作用，其依赖于ERK 1/2，（3）吗啡调节海马神经元中的miR-133 b，以及（4）δ阿片受体在吗啡诱导的miR-133 b调节中的作用。我们的结论是，miR-133 b水平的控制可能是吗啡成瘾的发展机制，或其他滥用药物，增加细胞外空间的多巴胺能水平。这些结果表明，miR-133 b可能是设计新的成瘾性疾病治疗方法的新靶点。
When we talk about drug addiction, we are really dealing with an extremely complex system in which there still remain many unknowns and where many empty spaces or missing links are still present. Recent studies have identified changes in the expression profiles of several specific miRNAs which affect the interactions between these molecules and their targets in various illnesses, including addiction, and which may serve as valuable targets for more efficient therapies. In this review, we summarize results which clearly demonstrate that several morphine-related miRNAs have roles in the mechanisms that define addiction. In this regard, morphine has been shown to have an important role in the regulation of different miRNAs, such as miR-let-7 [which works as a mediator of the movement of the mu opioid receptor (MOR) mRNA into P-bodies, leading to translational repression], miR-23b (involved in linking MOR expression and morphine treatment at the post-transcriptional level), and miR-190 (a key post-transcriptional repressor of neurogenic differentiation, NeuroD). Fentanyl increases NeuroD levels by reducing the amount of miR-190, but morphine does not affect the levels of NeuroD. We also discuss the relationship between morphine, miRNAs, and the immune system, based on the discovery that morphine treatment of monocytes led to a decrease in several anti-HIV miRNAs (mir-28, 125b, 150, and 382). This review is centered on miR-133b and its possible involvement in addiction through the effects of morphine. We establish the importance of miR-133b as a regulatory factor by summarizing its activity in different pathological processes, especially cancer. Using the zebrafish as a research model, we discuss the relationship between mir-133b, the dopaminergic system, and morphine, considering: (1) that morphine modulates the expression of miR-133b and of its target transcript Pitx3, (2) the role of the zebrafish mu opioid receptor (zfMOR) in morphine-induced regulation of miR-133b, which depends on ERK1/2, (3) that morphine regulates miR-133b in hippocampal neurons, and (4) the role of delta opioid receptors in morphine-induced regulation of miR-133b. We conclude that the control of miR-133b levels may be a mechanism for the development of addiction to morphine, or other drugs of abuse that increase dopaminergic levels in the extracellular space. These results show that miR-133b is a possible new target for the design of new treatments against addictive disorders.