A Comparative Review of microRNA Expression Patterns in Autism Spectrum Disorder.
A Comparative Review of microRNA Expression Patterns in Autism Spectrum Disorder.
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DOI：
10.3389/fpsyt.2016.00176
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发表时间：
2016
影响因子：
4.7
通讯作者：
Middleton FA
中科院分区：
文献类型：
--
作者：
Hicks SD;Middleton FA
自闭症谱系障碍（ASD）是一种神经发育障碍，其特征是在社交互动、沟通和行为方面存在广泛的缺陷。ASD有显著的遗传因素，但没有单一的基因变异能解释超过1%的发病率。转录后机制，如微小RNA（miRNAs）在不改变遗传密码的情况下调节基因表达。它们在发育中的大脑中含量丰富，在自闭症儿童中失调。自闭症患者的大脑、血液、唾液和嗅球前体细胞中miRNA的表达模式发生改变。miRNAs能够响应环境刺激调节广泛的分子通路，这使得它们在自闭症中成为一个引人关注的因素，自闭症是一种由遗传易感性和不明确的环境诱因所导致的疾病。此外，miRNAs的可获取性和细胞外稳定性使其成为生物标志物发现的理想候选对象。在此，我们讨论了在自闭症研究中重叠的27种miRNAs，包括在3项或更多研究中被确定的3种miRNAs（miR - 23a、miR - 146a和miR - 106b）。这27种miRNAs共有1245个高可信度的mRNA靶点，其中相当数量在大脑中表达。此外，这些mRNA靶点显示出自闭症相关基因的过度表达以及神经营养信号分子的富集。脑源性神经营养因子是一种参与海马神经发生且在自闭症中发生改变的分子，是所关注的27种miRNAs中的6种的靶点。这种神经营养通路代表了一种有趣的机制，通过该机制，miRNA信号的扰动可能会影响自闭症儿童的中枢神经系统发育。
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by a wide spectrum of deficits in social interaction, communication, and behavior. There is a significant genetic component to ASD, yet no single gene variant accounts for >1% of incidence. Posttranscriptional mechanisms such as microRNAs (miRNAs) regulate gene expression without altering the genetic code. They are abundant in the developing brain and are dysregulated in children with ASD. Patterns of miRNA expression are altered in the brain, blood, saliva, and olfactory precursor cells of ASD subjects. The ability of miRNAs to regulate broad molecular pathways in response to environmental stimuli makes them an intriguing player in ASD, a disorder characterized by genetic predisposition with ill-defined environmental triggers. In addition, the availability and extracellular stability of miRNAs make them an ideal candidate for biomarker discovery. Here, we discuss 27 miRNAs with overlap across ASD studies, including 3 miRNAs identified in 3 or more studies (miR-23a, miR-146a, and miR-106b). Together, these 27 miRNAs have 1245 high-confidence mRNA targets, a significant number of which are expressed in the brain. Furthermore, these mRNA targets demonstrate over-representation of autism-related genes with enrichment of neurotrophic signaling molecules. Brain-derived neurotrophic factor, a molecule involved in hippocampal neurogenesis and altered in ASD, is targeted by 6 of the 27 miRNAs of interest. This neurotrophic pathway represents one intriguing mechanism by which perturbations in miRNA signaling might influence central nervous system development in children with ASD.
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