Microarray expression profile analysis of long non-coding RNAs in optineurin E50K mutant transgenic mice.
Microarray expression profile analysis of long non-coding RNAs in optineurin E50K mutant transgenic mice.
复制标题
optineurin E50K突变转基因小鼠长非编码RNA的微阵列表达谱分析
DOI：
10.3892/mmr.2017.6722
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发表时间：
2017-08
影响因子：
3.4
通讯作者：
Yuan H
中科院分区：
文献类型：
--
作者：
Li Y;Jin L;Dong A;Zhou X;Yuan H
长链非编码RNA（lncRNA）的生物学作用涉及多种细胞过程并导致人类疾病。视神经磷酸酶（OPTN）基因突变，包括编码氨基酸取代的E50 K，与原发性开角型青光眼（POAG）相关。本研究旨在鉴定OPTN（E50K）转基因小鼠相关lncRNA，并探讨其在POAG发病机制中的作用。分别收集来自6只OPTN（E50K）转基因和野生型小鼠的视网膜，并使用微阵列分析进行lncRNA表达谱分析。基于Pearson相关分析，构建了lncRNA和mRNA共表达网络。使用基因本体论（GO）和京都基因和基因组百科全书对lncRNA和共表达mRNA进行富集分析以鉴定相关的生物模块和病理途径。利用基因集富集分析的计算方法预测差异表达lncRNA的GO生物学过程（BP）。共有69个lncRNA在OPTN（E50K）转基因小鼠和野生型小鼠之间显示出差异表达，其中包括37个下调和32个上调的lncRNA。途径分析表明，lncRNA与mRNA共表达的富集在mRNA监视和RNA转运途径。此外，在GO BP中注释了8个lncRNA，并且这8个lncRNA中的2个，ASMM10P055228和ASMM10P040128，注释了氧化应激诱导的细胞死亡的负调节和细胞凋亡的执行阶段的调节。这些结果表明，lncRNA在OPTN（E50K）转基因小鼠和野生型小鼠的视网膜中存在差异表达，这可能在OPTN（E50K）突变引起的POAG的发病机制中起重要作用。
The biological role of long non-coding RNAs (lncRNAs) involves various cellular processes and leads to human diseases. Mutations in the optineurin (OPTN) gene, including E50K, which encodes an amino acid substitution, have been associated with primary open angle glaucoma (POAG). The present study was designed to identify lncRNAs associated with OPTN (E50K) transgenic mice and investigate its functions in the pathogenesis of POAG. The retinas from six OPTN (E50K) transgenic and wild-type mice were collected separately, and lncRNA expression profiling was performed using microarray analysis. Based on Pearson's correlation analysis, an lncRNA and mRNA co-expression network was constructed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of the lncRNAs and coexpressed mRNAs was used to identify the associated biological modules and pathological pathways. The GO biological processes (BPs) of the differentially expressed lncRNAs were predicted using a computational method of gene set enrichment analysis. A total of 69 lncRNAs showed differential expression between the OPTN (E50K) transgenic mice and wild-type mice, which included 37 downregulated and 32 upregulated lncRNAs. The pathway analysis revealed that the lncRNAs coexpressed with mRNAs were enriched in mRNA surveillance and RNA transport pathways. In addition, eight lncRNAs were annotated in the GO BPs, and two of these eight lncRNAs, ASMM10P055228 and ASMM10P040128, were annotated with the negative regulation of oxidative stress-induced cell death and regulation of execution phase of apoptosis. These results showed that lncRNAs were differentially expressed in the retinas between OPTN (E50K) transgenic and wild-type mice, and this may be important in the pathogenesis of POAG caused by the OPTN (E50K) mutation.
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影响因子：
56.9
作者：
Rezaie, T;Child, A;Sarfarazi, M
通讯作者：
Sarfarazi, M
影响因子：
4.4
作者：
Leung, YF;Fan, BJ;Pang, CP
通讯作者：
Pang, CP
影响因子：
3.5
作者：
Chi ZL;Akahori M;Obazawa M;Minami M;Noda T;Nakaya N;Tomarev S;Kawase K;Yamamoto T;Noda S;Sasaoka M;Shimazaki A;Takada Y;Iwata T
通讯作者：
Iwata T
影响因子：
13.7
作者：
Iwase, A;Suzuki, Y;Kitazawa, Y
通讯作者：
Kitazawa, Y
影响因子：
4.1
作者：
Quigley, HA;Broman, AT
通讯作者：
Broman, AT