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与股骨头创伤性骨坏死中泛素蛋白酶体系统相关的微小RNA的生物信息学分析

Bioinformatics analysis of microRNA linked to ubiquitin proteasome system in traumatic osteonecrosis of the femoral head.

作者信息

Chen Ning, Xiao Bolian, Wang Shiying, Wei Biaofang

机构信息

Guangzhou University of Chinese Medicine, Guangzhou, Guangdong.

Department of Femoral Head, Linyi People's Hospital, Linyi, Shandong, China.

出版信息

Medicine (Baltimore). 2020 Aug 14;99(33):e21706. doi: 10.1097/MD.0000000000021706.

Abstract

MicroRNAs (miRNAs) have been suggested to act critical roles in the pathophysiology of traumatic osteonecrosis of the femoral head (TONFH). Unfortunately, their roles in the development of TONFH are still ambiguous. The purpose of this study is to identify promising miRNA biomarkers in traumatic osteonecrosis development.We conducted a comprehensive bioinformatics analysis using microarray datasets downloaded from the Gene Expression Omnibus database, and compared the expression of miRNAs in the serum of TONFH patients with controls. Next, we performed target prediction, function enrichment analysis, and protein-protein interaction network analysis based on differentially expressed (DE) miRNAs.We identified 26 DE miRNAs that may contribute to the pathophysiology of TONFH. The miRNAs were linked to ubiquitin proteasome system including conjugating protein ligase activity, ubiquitin-protein ligase activity and ubiquitin mediated proteolysis 5 pathway, and we exposed miR-181a-5p and miR-140-5p as promising biomarkers in TONFH.A predicting model consisting of 5 miRNAs may help discriminating high-risk patients who might develop TONFH after femur neck fracture. Among DE miRNAs, MiR-181a-5p and miR-140-5p may contribute to the development femoral head osteonecrosis after femur neck fracture via ubiquitin proteasome system.

摘要

微小RNA(miRNA)已被认为在股骨头创伤性骨坏死(TONFH)的病理生理学中起关键作用。不幸的是,它们在TONFH发展中的作用仍不明确。本研究的目的是确定创伤性骨坏死发展中有前景的miRNA生物标志物。我们使用从基因表达综合数据库下载的微阵列数据集进行了全面的生物信息学分析,并比较了TONFH患者与对照组血清中miRNA的表达。接下来,我们基于差异表达(DE)的miRNA进行了靶标预测、功能富集分析和蛋白质-蛋白质相互作用网络分析。我们鉴定出26种可能与TONFH病理生理学相关的DE miRNA。这些miRNA与泛素蛋白酶体系统相关,包括缀合蛋白连接酶活性、泛素-蛋白连接酶活性和泛素介导的蛋白水解5途径,并且我们发现miR-181a-5p和miR-140-5p是TONFH中有前景的生物标志物。一个由5种miRNA组成的预测模型可能有助于区分股骨颈骨折后可能发生TONFH的高危患者。在DE miRNA中,MiR-181a-5p和miR-140-5p可能通过泛素蛋白酶体系统促进股骨颈骨折后股骨头坏死的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dfa/7437855/1821cf905b07/medi-99-e21706-g002.jpg

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