Abstract：
Traumatic brain injury (TBI) refers to brain dysfunction with or without traumatic structural injury induced by an external force. Nevertheless, the molecular mechanism of TBI remains undefined. Differentially expressed (DE) lncRNAs, DEmRNAs and DEmiRNAs were selected between human TBI tissues and the adjacent histologically normal tissue by high-throughput sequencing. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis of overlapping DEmRNAs between predicted mRNAs of DEmiRNAs and DEmRNAs. The competitive endogenous RNA (ceRNA) network of lncRNA-miRNA-mRNA was established in light of the ceRNA theory. In the ceRNA network, the key lncRNAs were screened out. Then key lncRNAs related ceRNA subnetwork was constructed. After that, qRT-PCR was applied to validate the expression levels of hub genes. 114 DElncRNAs, 1807 DEmRNAs and 6 DEmiRNAs were DE in TBI. The TBI-related ceRNA network was built with 73 lncRNA nodes, 81 mRNA nodes and 6 miRNAs. According to topological analysis, two hub lncRNAs (ENST00000562897 and ENST00000640877) were selected to construct the ceRNA subnetwork. Subsequently, key lncRNA-miRNA-mRNA regulatory axes constructed by two lncRNAs including ENST00000562897 and ENST00000640877, two miRNAs including miR-6721-5p and miR-129-1-3p, two mRNAs including ketohexokinase (KHK) and cyclic nucleotide-gated channel beta1 (CNGB1), were identified. Furthermore, qRT-PCR results displayed that the expression of ENST00000562897, KHK and CNGB1 were significantly decreased in TBI, while the miR-6721-5p expression levels were markedly increased in TBI. The results of our study reveal a new insight into understanding the ceRNA regulation mechanism in TBI and select key lncRNA-miRNA-mRNA axes for prevention and treatment of TBI.
摘要：
创伤性脑损伤（TBI）是指由外力引起的有或没有创伤性结构损伤的脑功能障碍。然而，TBI的分子机制尚不明确。差异表达（DE）lncRNAs，通过高通量测序在人TBI组织和邻近的组织学正常组织之间选择DEmRNA和DEmiRNAs。DEmiRNAs和DEmiRNAs的预测mRNAs之间的重叠DMRNAs的基因本体论富集分析和基因和基因组的京都百科全书途径分析。根据ceRNA理论，建立了lncRNA-miRNA-mRNA的竞争性内源RNA（ceRNA）网络。在ceRNA网络中，筛选出关键的lncRNAs。然后构建了关键的lncRNAs相关的ceRNA子网络。之后,应用qRT-PCR来验证hub基因的表达水平。114DElncRNAs,1807个DEmRNAs和6个DEmiRNAs在TBI中是DE的。与TBI相关的ceRNA网络由73个lncRNA节点组成，81个mRNA节点和6个miRNAs。根据拓扑分析,选择两个hublncRNAs(ENST00000562897和ENST00000640877)来构建ceRNA亚网络。随后，关键的lncRNA-miRNA-mRNA调控轴由两个lncRNA（包括ENST00000562897和ENST00000640877），两个miRNAs（包括miR-6721-5p和miR-129-1-3p）构建，两个mRNA，包括酮己糖激酶（KHK）和环核苷酸门控通道β1（CNGB1），已确定。此外，qRT-PCR成果显示ENST00000562897、KHK和CNGB1在TBI中的表达显著下降,而miR-6721-5p表达水平在TBI中显著升高。我们的研究结果揭示了理解TBI中ceRNA调控机制的新见解，并选择了预防和治疗TBI的关键lncRNA-miRNA-mRNA轴。
