Yan-Hui Shi1, Xin-Wei He1, Feng-Di Liu1, Yi-Sheng Liu1, Yue Hu1, Liang Shu1, Guo-Hong Cui1, Rong Zhao1, Lei Zhao1, Jing-Jing Su2, Jian-Ren Liu3. 1. Department of Neurology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Clinical Research Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. 2. Department of Neurology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Clinical Research Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. Electronic address: sujj112035@sh9hospital.org. 3. Department of Neurology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Clinical Research Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. Electronic address: liujr021@sjtu.edu.cn.
Abstract
BACKGROUNDS: The pathophysiology of hydrocephalus induced brain damage remains unclear. Long non-coding RNAs (lncRNAs) have been demonstrated to be implicated in many central nervous system diseases. However, the roles of lncRNAs in hydrocephalus injury are poorly understood. METHODS: The present study depicted the expression profiles of lncRNAs and messenger RNAs (mRNAs) in C57BL/6 mice with kaolin-induced hydrocephalus and saline controls using high-throughput RNA sequencing. Afterward, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to identify potential targets that correlated with hydrocephalus. In addition, co-expression networks and cis- and trans-regulation were predicted using bioinformatics methods. Finally, representative lncRNAs and mRNAs were further validation using quantitative real-time polymerase chain reaction. RESULTS: A total of 1575 lncRNAs and 1168 mRNAs were differentially expressed (DE) in hydrocephalus. GO and KEGG analyses indicated several immune and inflammatory response-associated pathways may be important in the hydrocephalus. Besides, functional enrichment analysis based on co-expression network showed several similar pathways, such as chemokine signaling pathway, phagosome, MAPK signaling pathway and complement and coagulation cascade. Cis-regulation prediction revealed 5 novel lncRNAs might regulate their nearby coding genes, and trans-regulation revealed several lncRNAs participate in pathways regulated by transcription factors, including BPTF, FOXM1, NR5A2, P2RX5, and NR6A1. CONCLUSIONS: In conclusion, our results provide candidate genes involved in hydrocephalus and suggest a new perspective on the modulation of lncRNAs in hydrocephalus.
BACKGROUNDS: The pathophysiology of hydrocephalus induced brain damage remains unclear. Long non-coding RNAs (lncRNAs) have been demonstrated to be implicated in many central nervous system diseases. However, the roles of lncRNAs in hydrocephalus injury are poorly understood. METHODS: The present study depicted the expression profiles of lncRNAs and messenger RNAs (mRNAs) in C57BL/6 mice with kaolin-induced hydrocephalus and saline controls using high-throughput RNA sequencing. Afterward, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to identify potential targets that correlated with hydrocephalus. In addition, co-expression networks and cis- and trans-regulation were predicted using bioinformatics methods. Finally, representative lncRNAs and mRNAs were further validation using quantitative real-time polymerase chain reaction. RESULTS: A total of 1575 lncRNAs and 1168 mRNAs were differentially expressed (DE) in hydrocephalus. GO and KEGG analyses indicated several immune and inflammatory response-associated pathways may be important in the hydrocephalus. Besides, functional enrichment analysis based on co-expression network showed several similar pathways, such as chemokine signaling pathway, phagosome, MAPK signaling pathway and complement and coagulation cascade. Cis-regulation prediction revealed 5 novel lncRNAs might regulate their nearby coding genes, and trans-regulation revealed several lncRNAs participate in pathways regulated by transcription factors, including BPTF, FOXM1, NR5A2, P2RX5, and NR6A1. CONCLUSIONS: In conclusion, our results provide candidate genes involved in hydrocephalus and suggest a new perspective on the modulation of lncRNAs in hydrocephalus.