Li Chen, Li Jianqing, Lu Peirong
Department of Ophthalmology, the First Affiliated Hospital of Soochow University, Shizi Street 188, Suzhou, 21006, Jiangsu Province, China.
Acta Biochim Pol. 2021 Nov 3;68(4):733-737. doi: 10.18388/abp.2020_5632.
Cataract is a common and frequently occurring disease in the elderly. The Brahma-related gene 1 (Brg1) is believed to be related to the formation of cataract, but its mechanisms still remain unclear. This study aimed to investigate how a Brg1 mutation affects lens development and promotes the formation of cataract in mice.
We used mRNA profiles downloaded from the Gene Expression Omnibus (GEO) database to compare the tissue samples of lenses from 4 dominant-negative Brg1(dnBrg1) transgenic mice and 4 wild-type mice. Then, the NetworkAnalyst online tool was employed to screen for the significantly differentially expressed genes (DEGs). Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome pathway analysis were examined in DEGs by using Metascape. In addition, we applied the STRING online tool and Cytoscape software to build the protein-protein interaction (PPI) network. Finally, the CytoNCA plug-in was used to choose the central modules from the PPI network.
323 DEGs were filtered in total, 222 of which were up-regulated genes and enriched in the cell cycle process regulation, mitotic G1-G1/S phase, mRNA splicing, etc., while 101 of which were down-regulated genes and enriched in the organ hydroxy compound transport, synaptic vesicle cycle and neuron migration. Within this network of PPI, we found that the heat shock protein 90 alpha (cytosolic), class B member 1 (HSP90ab1), the polymerase (RNA) II (DNA directed) polypeptide E (Polr2e), the cell division cycle 20 (Cdc20) and the polymerase (RNA) II (DNA directed) polypeptide C (Polr2c) had higher connectivity degrees and may interact and influence each other.
The Brg1 mutation affected expression of various genes in mice, such as HSP90ab1, Polr2e, Cdc20, and Polr2c. These genes may have some effects on the occurrence and development of cataract, and may serve as potential therapeutic targets for the cataract treatment.
白内障是老年人常见且多发病。与婆罗门相关基因1（Brg1）被认为与白内障的形成有关，但其机制仍不清楚。本研究旨在探讨Brg1突变如何影响小鼠晶状体发育并促进白内障形成。
我们使用从基因表达综合数据库（GEO）下载的mRNA谱，比较4只显性负性Brg1（dnBrg1）转基因小鼠和4只野生型小鼠的晶状体组织样本。然后，使用在线工具NetworkAnalyst筛选显著差异表达基因（DEG）。通过Metascape对DEG进行基因本体（GO）注释、京都基因与基因组百科全书（KEGG）和Reactome通路分析。此外，我们应用STRING在线工具和Cytoscape软件构建蛋白质-蛋白质相互作用（PPI）网络。最后，使用CytoNCA插件从PPI网络中选择中心模块。
共筛选出323个DEG，其中222个为上调基因，富集于细胞周期进程调控、有丝分裂G1-G1/S期、mRNA剪接等；101个为下调基因，富集于器官羟基化合物转运、突触小泡循环和神经元迁移。在这个PPI网络中，我们发现热休克蛋白90α（胞质）B类成员1（HSP90ab1）、聚合酶（RNA）II（DNA定向）多肽E（Polr2e）、细胞分裂周期20（Cdc20）和聚合酶（RNA）II（DNA定向）多肽C（Polr2c）具有较高的连接度，可能相互作用并相互影响。
Brg1突变影响小鼠多种基因的表达，如HSP90ab1、Polr2e、Cdc20和Polr2c。这些基因可能对白内障的发生发展有一定影响，可能成为白内障治疗的潜在靶点。
