MiR-190a potentially ameliorates postoperative cognitive dysfunction by regulating Tiam1

Abstract

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 coexpression 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.

Suppression of Inflammatory Cardiac Cytokine Network in Rats with Untreated Obesity and Pre-Diabetes by AT2 Receptor Agonist NP-6A4

“…We found that miR-101b-3p abrogates cardiomyocyte hypertrophy and fibrosis (Pan et al, 2012;Lee et al, 2017) and miR-148b-3p, is downregulated in mitral regurgitation and heart failure (Chen et al, 2016; Figure 6A; Table 3). Literature also showed that miR-101b-3p suppresses Stc1 (Stanniocalcin 1) implicated in macrophage differentiation, preferentially M1 polarization, and contributes to the increase in expression of multiple inflammatory cytokines (Table 3; De Martino et al, 2009;Leung and Wong, 2021) Similarly, miR-190a-3p is shown to target and suppress Tiam1 that activates il17 promoter and increase inflammatory cytokines (Table 3; Kurdi et al, 2016. Liu et al, 2019.…”

Identification of the Potential Gene Regulatory Networks and Therapeutics in Aged Mice With Postoperative Neurocognitive Disorder

“…The miR-572 improves early postoperative cognitive dysfunction by down-regulating NCAM1 ( Yu et al, 2015 ). Meanwhile, the miR-190a improves postoperative cognitive dysfunction in mice by regulating the expression of Tiam1 ( Liu et al, 2019 ). The miRNA-146a protects mice from cognitive impairment caused by operation by inhibiting the neuroinflammation ( Chen L. et al, 2019 ).…”

“…Therefore, circRNAs may be related to the pathogenesis of PND ( Gao et al, 2020 ). Meanwhile, the up-regulated expression of miRNA-572 in hippocampal neurons contributes to the recovery of cognitive function in rats with PND ( Yu et al, 2015 ), and the miRNA-190a also plays a key role in the pathogenesis of PND ( Liu et al, 2019 ). However, the differential expression profiles and possible ceRNA networks caused by PND remains unclear.…”

Microarray Analysis Identifies Key Differentially Expressed Circular RNAs in Aged Mice With Postoperative Cognitive Dysfunction

“…The pathogenesis of POCD is complex and lacks effective diagnosis and treatment. Therefore, several recent studies have focused on the epigenetic regulation of the pathogenesis of POCD to discover potential therapies (Li et al, 2015;Liu et al, 2019;Zhong and Xu, 2019). miRNAs and lncRNAs in the brain have been reported to contribute to POCD Su et al, 2019).…”

“…Genome analysis has been used to identify functional genes in POCD for several years (Li et al, 2015). For example, Liu et al (2019) found that many miRNAs were differentially expressed between POCD and control-aged mice (Chen et al, 2019;Su et al, 2019). Furthermore, long non-coding RNAs (lncRNAs) were found to be differentially expressed in mRNAs and might contribute to POCD .…”