Integrative network analysis of N<sup>6</sup> methylation-related genes reveal potential therapeutic targets for spinal cord injury

Shanzheng Wang; Xinhui Xie; Chao Li; Jun Jia; Changhong Chen; Shanzheng Wang; Xinhui Xie; Chao Li; Jun Jia; Changhong Chen

doi:10.3934/mbe.2021405

Mathematical Biosciences and Engineering

2021, Volume 18, Issue 6: 8174-8187. doi: 10.3934/mbe.2021405

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Integrative network analysis of N⁶ methylation-related genes reveal potential therapeutic targets for spinal cord injury

1.
Department of Orthopaedics, Zhongda Hospital, Medical School of Southeast University, 87 Dingjiaqiao Road, Nanjing 210009, China
2.
Department of Orthopaedics, The 904^th Hospital of Joint Logistic Support Force, PLA, 101 Xingyuan North Road, Wuxi 214000, China
3.
Department of Orthopaedics, Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, 130 Renmin Middle Road, Jiangyin 214400, China

^† These authors contributed equally to this work.
Academic Editor: Xiaoqiang Sun

Received: 03 August 2021 Accepted: 09 September 2021 Published: 18 September 2021

The diagnosis of the severity of spinal cord injury (SCI) and the revelation of potential therapeutic targets are crucial for urgent clinical care and improved patient outcomes. Here, we analyzed the overall gene expression data in peripheral blood leukocytes during the acute injury phase collected from Gene Expression Omnibus (GEO) and identified six m6A regulators specifically expressed in SCI compared to normal samples. LncRNA-mRNA network analysis identified AKT2/3 and PIK3R1 related to m6A methylation as potential therapeutic targets for SCI and constructed a classifier to identify patients of SCI to assist clinical diagnosis. Moreover, FTO (eraser) and RBMX (reader) were found to be significantly down-regulated in SCI and the functional gene co-expressed with them was found to be involved in the signal transduction of multiple pathways related to nerve injury. Through the construction of the drug-target gene network, eight key genes were identified as drug targets and it was emphasized that fostamatinib can be used as a potential drug for the treatment of SCI. Taken together, our study characterized the pathogenesis and identified a potential therapeutic target of SCI providing theoretical support for the development of precision medicine.
- N⁶ methylation,
- spinal cord injury,
- lncRNA,
- therapeutic targets,
- network analysis
Citation: Shanzheng Wang, Xinhui Xie, Chao Li, Jun Jia, Changhong Chen. Integrative network analysis of N6 methylation-related genes reveal potential therapeutic targets for spinal cord injury[J]. Mathematical Biosciences and Engineering, 2021, 18(6): 8174-8187. doi: 10.3934/mbe.2021405

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Abstract

The diagnosis of the severity of spinal cord injury (SCI) and the revelation of potential therapeutic targets are crucial for urgent clinical care and improved patient outcomes. Here, we analyzed the overall gene expression data in peripheral blood leukocytes during the acute injury phase collected from Gene Expression Omnibus (GEO) and identified six m6A regulators specifically expressed in SCI compared to normal samples. LncRNA-mRNA network analysis identified AKT2/3 and PIK3R1 related to m6A methylation as potential therapeutic targets for SCI and constructed a classifier to identify patients of SCI to assist clinical diagnosis. Moreover, FTO (eraser) and RBMX (reader) were found to be significantly down-regulated in SCI and the functional gene co-expressed with them was found to be involved in the signal transduction of multiple pathways related to nerve injury. Through the construction of the drug-target gene network, eight key genes were identified as drug targets and it was emphasized that fostamatinib can be used as a potential drug for the treatment of SCI. Taken together, our study characterized the pathogenesis and identified a potential therapeutic target of SCI providing theoretical support for the development of precision medicine.

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