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小鼠创伤性脑损伤后lncRNA相关竞争性内源性RNA调控网络的构建

Construction of a lncRNA-associated competing endogenous RNA regulatory network after traumatic brain injury in mouse.

作者信息

Wang Siqi, Sun Yiyu, Hu Shaobo, Lou Cen, Pan Yuan-Bo

机构信息

Department of Nuclear Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, Zhejiang, China.

Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University, 639 Zhi Zao Ju Road, Shanghai, 200011, China.

出版信息

Mol Brain. 2022 May 2;15(1):40. doi: 10.1186/s13041-022-00925-8.

DOI:10.1186/s13041-022-00925-8
PMID:35501920
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9063179/
Abstract

Traumatic brain injury (TBI) is a major public health problem worldwide which causes high mortality and disability. Functioning as microRNA (miRNA) sponges, long non-coding RNA (lncRNA) regulates the expression of protein-coding genes in a competing endogenous RNA (ceRNA) network. However, the lncRNA-associated ceRNA in TBI remains unclear. In this study, we processed the raw SRR files of mice cortex samples of sham injury (n = 3) and TBI groups (n = 3) to count files. Then, the expression profiles of lncRNAs and mRNAs were identified, and 86 differentially expressed (DE) lncRNAs and 1201 DEmRNAs between sham and TBI groups were identified. The DEmRNAs were used to perform enrichment analyses. Next, a lncRNA-miRNA-mRNA regulatory ceRNA network was constructed. The network consisted of 23 mRNAs, 5 miRNAs and 2 lncRNAs. The expression alternations of the 5 miRNAs were validated via qRT-PCR. The subnetwork of hub lncRNA Neat1 was extracted. We identified a potential inflammatory associated regulatory axis: Neat1/miR-31-5p/Myd88 axis. The PPI network based on DEmRNA involved in ceRNA network was constructed PPI networks to identify the hub genes. Finally, DElncRNAs and DEmRNAs were selected randomly and validated by qRT-PCR. In conclusion, with the lncRNA-miRNA-mRNA ceRNA network provided above, we can improve our understanding of the regulatory mechanisms and interaction among lncRNAs, miRNAs and mRNAs in TBI process.

摘要

创伤性脑损伤(TBI)是全球范围内的一个重大公共卫生问题,会导致高死亡率和残疾率。长链非编码RNA(lncRNA)作为微小RNA(miRNA)海绵,在竞争性内源性RNA(ceRNA)网络中调节蛋白质编码基因的表达。然而,TBI中与lncRNA相关的ceRNA仍不清楚。在本研究中,我们对假损伤组(n = 3)和TBI组(n = 3)小鼠皮质样本的原始SRR文件进行处理以进行计数。然后,鉴定lncRNAs和mRNAs的表达谱,确定假手术组和TBI组之间有86个差异表达(DE)lncRNAs和1201个DEmRNAs。利用这些DEmRNAs进行富集分析。接下来,构建lncRNA-miRNA-mRNA调控ceRNA网络。该网络由23个mRNA、5个miRNA和2个lncRNA组成。通过qRT-PCR验证了5个miRNA的表达变化。提取了关键lncRNA Neat1的子网。我们鉴定出一条潜在的炎症相关调控轴:Neat1/miR-31-5p/Myd88轴。构建基于参与ceRNA网络的DEmRNA的蛋白质-蛋白质相互作用(PPI)网络以鉴定关键基因。最后,随机选择DElncRNAs和DEmRNAs并通过qRT-PCR进行验证。总之,通过上述lncRNA-miRNA-mRNA ceRNA网络,我们可以更好地理解TBI过程中lncRNAs、miRNAs和mRNAs之间的调控机制及相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fa8/9063179/02ad6cb79529/13041_2022_925_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fa8/9063179/45bad6cf7457/13041_2022_925_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fa8/9063179/6f0f5ff9f601/13041_2022_925_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fa8/9063179/b277d60dd2f6/13041_2022_925_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fa8/9063179/02ad6cb79529/13041_2022_925_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fa8/9063179/45bad6cf7457/13041_2022_925_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fa8/9063179/6f0f5ff9f601/13041_2022_925_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fa8/9063179/b277d60dd2f6/13041_2022_925_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fa8/9063179/02ad6cb79529/13041_2022_925_Fig4_HTML.jpg

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