Atypical miRNA expression in temporal cortex associated with dysregulation of immune, cell cycle, and other pathways in autism spectrum disorders.
Atypical miRNA expression in temporal cortex associated with dysregulation of immune, cell cycle, and other pathways in autism spectrum disorders.
复制标题
DOI：
10.1186/s13229-015-0029-9
复制
发表时间：
2015
期刊：
影响因子：
6.2
通讯作者：
Schumann CM
中科院分区：
文献类型：
--
作者：
Ander BP;Barger N;Stamova B;Sharp FR;Schumann CM
自闭症谱系障碍（ASD）可能涉及与大脑功能和发育相关的多个基因的失调。个体调控性小非编码RNA（sncRNA），包括microRNA（miRNA）的缺失可能对多种功能通路产生深远影响。我们评估了与ASD核心社交障碍相关的大脑区域，即上级颞沟（STS），是否比相邻但功能不同的初级听觉皮层（PAC）更能证明sncRNA的转录失调。我们测量了34例STS和PAC死后脑组织样本中sncRNA的表达水平，以发现ASD与对照组相比差异表达的sncRNA。对于差异表达的miRNA，我们进一步分析了它们预测的mRNA靶点，并对KEGG通路进行了功能过度表达分析，以检查它们的功能意义，并将我们的发现与ASD基因表达的改变进行比较。两种成熟的miRNAs（miR-4753- 5 p和miR-1）在ASD中相对于对照在STS中差异表达，四种成熟的miRNAs（miR-664- 3 p、miR-4709- 3 p、miR-4742- 3 p和miR-297）在PAC中差异表达。在这两个区域中，miRNA在功能上与各种神经系统、细胞周期和经典信号传导途径相关，包括先前与ASD有关的PI 3 K-Akt信号传导。免疫途径仅在STS中被破坏。snoRNA和pre-miRNA在ASD脑中也有差异表达。sncRNA的改变可能是自闭症分子通路失调的基础。ASD中的sncRNA转录异常在STS和PAC中是明显的，PAC是与核心行为障碍不直接相关的大脑区域。免疫途径中的miRNA的破坏，经常与ASD有关，是STS所独有的。本文的在线版本（doi：10.1186/s13229-015-0029-9）包含补充材料，可供授权用户使用。
Autism spectrum disorders (ASDs) likely involve dysregulation of multiple genes related to brain function and development. Abnormalities in individual regulatory small non-coding RNA (sncRNA), including microRNA (miRNA), could have profound effects upon multiple functional pathways. We assessed whether a brain region associated with core social impairments in ASD, the superior temporal sulcus (STS), would evidence greater transcriptional dysregulation of sncRNA than adjacent, yet functionally distinct, primary auditory cortex (PAC). We measured sncRNA expression levels in 34 samples of postmortem brain from STS and PAC to find differentially expressed sncRNA in ASD compared with control cases. For differentially expressed miRNA, we further analyzed their predicted mRNA targets and carried out functional over-representation analysis of KEGG pathways to examine their functional significance and to compare our findings to reported alterations in ASD gene expression. Two mature miRNAs (miR-4753-5p and miR-1) were differentially expressed in ASD relative to control in STS and four (miR-664-3p, miR-4709-3p, miR-4742-3p, and miR-297) in PAC. In both regions, miRNA were functionally related to various nervous system, cell cycle, and canonical signaling pathways, including PI3K-Akt signaling, previously implicated in ASD. Immune pathways were only disrupted in STS. snoRNA and pre-miRNA were also differentially expressed in ASD brain. Alterations in sncRNA may underlie dysregulation of molecular pathways implicated in autism. sncRNA transcriptional abnormalities in ASD were apparent in STS and in PAC, a brain region not directly associated with core behavioral impairments. Disruption of miRNA in immune pathways, frequently implicated in ASD, was unique to STS. The online version of this article (doi:10.1186/s13229-015-0029-9) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
6.2
作者：
Edmonson C;Ziats MN;Rennert OM
通讯作者：
Rennert OM
影响因子：
21.1
作者：
Li, Yongkui;Xie, Jiajia;Zhu, Ying
通讯作者：
Zhu, Ying
影响因子：
4.8
作者：
Follert P;Cremer H;Béclin C
通讯作者：
Béclin C
影响因子：
11.1
作者：
Holt, Richard;Monaco, Anthony P.
通讯作者：
Monaco, Anthony P.
影响因子：
3.7
作者：
Kong SW;Collins CD;Shimizu-Motohashi Y;Holm IA;Campbell MG;Lee IH;Brewster SJ;Hanson E;Harris HK;Lowe KR;Saada A;Mora A;Madison K;Hundley R;Egan J;McCarthy J;Eran A;Galdzicki M;Rappaport L;Kunkel LM;Kohane IS
通讯作者：
Kohane IS