Peng Peng1, Bin Zhang1, Jingyuan Huang1, Cong Xing1, Weixiao Liu1, Chao Sun1, Wei Guo2, Shengyu Yao1, Wendong Ruan1, Guangzhi Ning1, Xiaohong Kong3, Shiqing Feng4. 1. Department of Orthopedics, Tianjin Medical University General Hospital, No.154 Anshan Road, Heping District, Tianjin 300052, PR China; International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, PR China. 2. Department of Orthopedics, Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine (Cangzhou No. 2 Hospital), Cangzhou, PR China. 3. 221 Laboratory, School of Medicine, Nankai University, Tianjin, PR China. 4. Department of Orthopedics, Tianjin Medical University General Hospital, No.154 Anshan Road, Heping District, Tianjin 300052, PR China; International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, PR China. Electronic address: sqfeng@tmu.edu.cn.
Abstract
AIMS: Many studies have demonstrated that circRNAs are closely associated with human diseases. Nonetheless, the potential mechanism by which circRNAs impacts spinal cord injury (SCI) is not fully understood. The aim of this study was to explore the regulatory roles of circRNAs in SCI. MAIN METHODS: The sequencing data of circRNA, miRNA and mRNA were obtained from Gene Expression Omnibus (GEO) datasets. Candidates were identified to construct a circRNA-miRNA-mRNA network based on circRNA-miRNA interactions and miRNA-mRNA interactions. Protein-protein interactions (PPI) analysis was performed to determine hub genes, and a connectivity map (CMap) analysis was applied to determine potential therapeutic targets for SCI. KEY FINDINGS: A total of 1656 differentially expressed circRNAs (DEcircRNAs), 71 differentially expressed miRNAs (DEmiRNAs) and 2782 differentially expressed mRNAs (DEmRNAs) were identified. We integrated four overlapped circRNAs, six miRNAs and 101 target mRNAs into a circRNA-miRNA-mRNA network. We next identified two hub genes (DDIT4, EZR) based on the PPI network and identified five circRNA-miRNA-hub gene regulatory axes. In addition, we discovered three chemicals (tanespimycin, fulvestrant, carbamazepine) as potential treatment options for SCI. SIGNIFICANCE: Our study suggests a regulatory role for circRNAs in the pathogenesis and treatment of SCI from the view of a competitive endogenous RNA (ceRNA) network.
AIMS: Many studies have demonstrated that circRNAs are closely associated with human diseases. Nonetheless, the potential mechanism by which circRNAs impacts spinal cord injury (SCI) is not fully understood. The aim of this study was to explore the regulatory roles of circRNAs in SCI. MAIN METHODS: The sequencing data of circRNA, miRNA and mRNA were obtained from Gene Expression Omnibus (GEO) datasets. Candidates were identified to construct a circRNA-miRNA-mRNA network based on circRNA-miRNA interactions and miRNA-mRNA interactions. Protein-protein interactions (PPI) analysis was performed to determine hub genes, and a connectivity map (CMap) analysis was applied to determine potential therapeutic targets for SCI. KEY FINDINGS: A total of 1656 differentially expressed circRNAs (DEcircRNAs), 71 differentially expressed miRNAs (DEmiRNAs) and 2782 differentially expressed mRNAs (DEmRNAs) were identified. We integrated four overlapped circRNAs, six miRNAs and 101 target mRNAs into a circRNA-miRNA-mRNA network. We next identified two hub genes (DDIT4, EZR) based on the PPI network and identified five circRNA-miRNA-hub gene regulatory axes. In addition, we discovered three chemicals (tanespimycin, fulvestrant, carbamazepine) as potential treatment options for SCI. SIGNIFICANCE: Our study suggests a regulatory role for circRNAs in the pathogenesis and treatment of SCI from the view of a competitive endogenous RNA (ceRNA) network.
Authors: Yu Yao; Xin Zhang; Jun Xu; Feng Gao; Yanni Wu; Xintao Cui; Li Wei; Jie Jiang; Xintao Wang Journal: Am J Transl Res Date: 2022-01-15 Impact factor: 4.060