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晶状体上皮细胞中调控的circRNA-miRNA-mRNA网络的分析及综合分析

Profiling and Integrated Analysis of the -regulated circRNA-miRNA-mRNA Network in Lens Epithelial Cells.

作者信息

Wang Ying, Zhang Guowei, Li Pengfei, Kang Lihua, Qin Bai, Cao Yu, Luo Jiawei, Chen Xiaojuan, Qin Miaomiao, Guan Huaijin

机构信息

Eye Institute, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.

出版信息

Curr Eye Res. 2021 Sep;46(9):1341-1352. doi: 10.1080/02713683.2021.1896742. Epub 2021 Mar 16.

Abstract

: To explore the regulatory role of ERCC6 in the circRNA-miRNA-mRNA network using a cellular ERCC6 overexpression model (OE-ERCC6) in lens epithelial cells.: The expression profiles of circRNAs, miRNAs and mRNAs were determined by RNA-seq, and a regulatory circRNA-miRNA-mRNA network was constructed via bioinformatics. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used for the functional annotation of circRNA host genes, differentially expressed (DE) genes, and miRNA targets.: The DE molecules between the OE-ERCC6 and control groups included 269 circRNAs, 241 miRNAs and 3500 mRNAs. We validated 5 selected DE reads of circRNAs (hsa_circ_0001009, hsa_circ_0002024, hsa_circ_0004592, hsa_circ_0001900 and hsa_circ_0001017). Subsequent bioinformatics analysis revealed that the DE circRNAs are mainly involved in oxidative stress- and cell death-related signaling pathways. Finally, a circRNA-miRNA-mRNA network focusing on DNA damage and cell death, which involved 5 circRNAs, 13 miRNAs and 107 mRNAs, was constructed.: We constructed a circRNA-miRNA-mRNA network that is regulated by ERCC6. DE circRNAs have the potential to become therapeutic targets related to the lens lesions observed in ARC. The establishment of related in vivo and in vitro models could be a future direction to confirm these hypotheses.

摘要

利用晶状体上皮细胞的细胞外切修复交叉互补基因6(ERCC6)过表达模型(OE-ERCC6)探索ERCC6在circRNA-miRNA-mRNA网络中的调控作用。

通过RNA测序确定circRNA、miRNA和mRNA的表达谱,并通过生物信息学构建调控性circRNA-miRNA-mRNA网络。采用基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析对circRNA宿主基因、差异表达(DE)基因和miRNA靶标进行功能注释。

OE-ERCC6组与对照组之间的DE分子包括269个circRNA、241个miRNA和3500个mRNA。我们验证了5个选定的circRNA的DE读数(hsa_circ_0001009、hsa_circ_0002024、hsa_circ_0004592、hsa_circ_0001900和hsa_circ_0001017)。随后的生物信息学分析表明,DE circRNA主要参与氧化应激和细胞死亡相关的信号通路。最后,构建了一个聚焦于DNA损伤和细胞死亡的circRNA-miRNA-mRNA网络,该网络涉及5个circRNA、13个miRNA和107个mRNA。

我们构建了一个受ERCC6调控的circRNA-miRNA-mRNA网络。DE circRNA有可能成为与常染色体隐性遗传性脑白质营养不良(ARC)中观察到的晶状体病变相关的治疗靶点。建立相关的体内和体外模型可能是未来证实这些假设的一个方向。

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