MiR-190a Potentially Ameliorates Postoperative Cognitive Dysfunction by Regulating Tiam1
| Autor: | Jingjing Li, jiangbei cao, Ai-sheng Hou, Kaimeng Niu, Ying Guo, Yunlong Ma, Yongyi Zhang, Qiang Liu, Hao Li, Yinghao Yao |
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| Rok vydání: | 2019 |
| Předmět: |
0106 biological sciences
Male lcsh:QH426-470 lcsh:Biotechnology Hippocampus Biology Bioinformatics Proteomics 01 natural sciences 03 medical and health sciences Mice Neurocognitive disorders Postoperative Cognitive Complications lcsh:TP248.13-248.65 microRNA Genetics medicine Animals Gene Regulatory Networks T-Lymphoma Invasion and Metastasis-inducing Protein 1 Animal model Maze Learning Gene POCD 030304 developmental biology 0303 health sciences miR-190a Brain medicine.disease Mice Inbred C57BL MicroRNAs lcsh:Genetics Real-time polymerase chain reaction DNA microarray Transcriptome Neurocognitive Postoperative cognitive dysfunction 010606 plant biology & botany Biotechnology Research Article |
| Zdroj: | BMC Genomics, Vol 20, Iss 1, Pp 1-12 (2019) BMC Genomics |
| DOI: | 10.21203/rs.2.10148/v4 |
| Popis: | Background Postoperative cognitive dysfunction (POCD) affects a large number of post-surgery patients, especially for the elderly. However, the etiology of this neurocognitive disorder is largely unknown. Even if several studies have reported a small number of miRNAs as the essential modulatory factors in POCD, these findings are still rather limited. The aim of current study was to screen the POCD-related miRNAs in the hippocampus tissues and investigate the target genes of differentially expressed miRNAs and their biological functions underlying POCD pathophysiology. Methods The miRNA microarray was used to find the abnormal expression of miRNAs in the hippocampus tissues from the POCD model mice to normal mice (Discovery cohort, 3 vs 3). The nominal significant results were validated in an independent sample of hippocampus tissues of 10 mice based on same miRNA microarray (Replication cohort, 5 vs 5). Expression level of the most significantly abnormal miRNA was further validated by real-time quantitative polymerase chain reaction (PCR). To determine the expression pattern among miRNAs and genes and detect the interactions, we conducted a weighted gene co-expression network analysis (WGCNA) in the miRNAs and genes expression data from hippocampus tissue of wild type mice (n = 24). The target genes of miRNAs were predicted using the miRWalk3.0 software. Furthermore, we used the ClueGO software to decipher the pathways network and reveal the biological functions of target genes of miRNAs. Results We found that nine miRNAs showed significant associations with POCD in both datasets. Among these miRNAs, mmu-miR-190a-3p was the most significant one. By performing WGCNA analysis, we found 25 co-expression modules, of which mmu-miR-190a-3p was significantly anti-correlated with red module. Moreover, in the red module, 314 genes were significantly enriched in four pathways such as axon guidance and calcium signaling pathway, which are well-documented to be associated with psychiatric disorders and brain development. Also, 169 of the 314 genes were highly correlated with mmu-miR-190a-3p, and four genes (Sphkap, Arhgef25, Tiam1, and Ntrk3) had putative binding sites at 3′-UTR of mmu-miR-190a-3p. Based on protein-protein network analysis, we detected that Tiam1 was a central gene regulated by the mmu-miR-190a-3p. Conclusions Taken together, we conclude that mmu-miR-190a-3p is involved in the etiology of POCD and may serve as a novel predictive indicator for POCD. Electronic supplementary material The online version of this article (10.1186/s12864-019-6035-0) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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