hsa-miR-3177-5p and hsa-miR-3178 Inhibit 5-HT1A Expression by Binding the 3′-UTR Region in vitro

Wu, Xue; Ding, Mei; Liu, Yi; Xia, Xi; Xu, Feng‐ling; Yao, Jun; Wang, Baojie

doi:10.3389/fnmol.2019.00013

Cited by 9 publications

(5 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In thyroid disorders, such as hyper- or hypothyroidism, variations of nucleosome assembly may affect the expression of genes related to TH synthesis and metabolism. In psychiatric disorders, such as depression, changes in nucleosome assembly may affect the expression of genes related to neurotransmitter systems, including the serotonin delivery pathway ( 57 ). Lipoprotein particle binding involved the interaction of specific proteins with lipoproteins, such as low-density lipoprotein (LDL) or high-density lipoprotein (HDL) ( 58 ).…”

Section: Discussionmentioning

confidence: 99%

Shared genetic links between hypothyroidism and psychiatric disorders: evidence from a comprehensive genetic analysis

Zhou,

Zhu

2024

Front. Endocrinol.

View full text Add to dashboard Cite

BackgroundEpidemiologic studies have suggested co-morbidity between hypothyroidism and psychiatric disorders. However, the shared genetic etiology and causal relationship between them remain currently unclear.MethodsWe assessed the genetic correlations between hypothyroidism and psychiatric disorders [anxiety disorders (ANX), schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP)] using summary association statistics from genome-wide association studies (GWAS). Two disease-associated pleiotropic risk loci and genes were identified, and pathway enrichment, tissue enrichment, and other analyses were performed to determine their specific functions. Furthermore, we explored the causal relationship between them through Mendelian randomization (MR) analysis.ResultsWe found significant genetic correlations between hypothyroidism with ANX, SCZ, and MDD, both in the Linkage disequilibrium score regression (LDSC) approach and the high-definition likelihood (HDL) approach. Meanwhile, the strongest correlation was observed between hypothyroidism and MDD (LDSC: rg=0.264, P=7.35×10-12; HDL: rg=0.304, P=4.14×10-17). We also determined a significant genetic correlation between MDD with free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels. A total of 30 pleiotropic risk loci were identified between hypothyroidism and psychiatric disorders, of which the 15q14 locus was identified in both ANX and SCZ (P values are 6.59×10-11 and 2.10×10-12, respectively) and the 6p22.1 locus was identified in both MDD and SCZ (P values are 1.05×10-8 and 5.75×10-14, respectively). Sixteen pleiotropic risk loci were identified between MDD and indicators of thyroid function, of which, four loci associated with MDD (1p32.3, 6p22.1, 10q21.1, 11q13.4) were identified in both FT4 normal level and Hypothyroidism. Further, 79 pleiotropic genes were identified using Magma gene analysis (P<0.05/18776 = 2.66×10-6). Tissue-specific enrichment analysis revealed that these genes were highly enriched into six brain-related tissues. The pathway analysis mainly involved nucleosome assembly and lipoprotein particles. Finally, our two-sample MR analysis showed a significant causal effect of MDD on the increased risk of hypothyroidism, and BIP may reduce TSH normal levels.ConclusionsOur findings not only provided evidence of a shared genetic etiology between hypothyroidism and psychiatric disorders, but also provided insights into the causal relationships and biological mechanisms that underlie their relationship. These findings contribute to a better understanding of the pleiotropy between hypothyroidism and psychiatric disorders, while having important implications for intervention and treatment goals for these disorders.

show abstract

Section: Discussionmentioning

confidence: 99%

Shared genetic links between hypothyroidism and psychiatric disorders: evidence from a comprehensive genetic analysis

Zhou,

Zhu

2024

Front. Endocrinol.

View full text Add to dashboard Cite

show abstract

“…Thus, BEST1 is likely to be involved in the progression of atherosclerotic inflammation, just like the role of BEST3 in the endothelial inflammatory response. We also predicted that BEST1 could be targeted by hsa-miR-3177-5p, which has been shown to have important regulatory effects on the expression of the 5-HT1A receptor in HEK-293 cells [33]. The 5-HT1A receptor is a subtype of serotonin receptor system (5-HT receptor), and serotonin modulates vascular tonus and mediates development and rupture of atherosclerotic plaques [34,35].…”

Section: Discussionmentioning

confidence: 99%

Underlying Genes Involved in Atherosclerotic Macrophages: Insights from Microarray Data Mining

Wang

Zhang

et al. 2019

Med Sci Monit

View full text Add to dashboard Cite

Background: In an atherosclerotic artery wall, monocyte-derived macrophages are the principal mediators that respond to pathogens and inflammation. The present study aimed to investigate potential genetic changes in gene expression between normal tissue-resident macrophages and atherosclerotic macrophages in the human body. Material/Methods: The expression profile data of GSE7074 acquired from the Gene Expression Omnibus (GEO) database, which includes the transcriptome of 4 types of macrophages, was downloaded. Differentially expressed genes (DEGs) were identified using R software, then we performed functional enrichment, protein-protein interaction (PPI) network construction, key node and module analysis, and prediction of microRNAs (miRNAs)/transcription factors (TFs) targeting genes. Results: After data processing, 236 DEGs were identified, including 21 upregulated genes and 215 downregulated genes. The DEG set was enriched in 22 significant Gene Ontology (GO) terms and 25 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and the PPI network constructed with these DEGs comprised 6 key nodes with degrees ³8. Key nodes in the PPI network and simultaneously involved in the prime modules, including rhodopsin (RHO), coagulation factor V (F5), and bestrophin-1 (BEST1), are promising for the prediction of atherosclerotic plaque formation. Furthermore, in the miRNA/TF-target network, hsa-miR-3177-5p might be involved in the pathogenesis of atherosclerosis via regulating BEST1, and the transcription factor early growth response-1 (EGR1) was found to be a potential promoter in atherogenesis. Conclusions: The identified key hub genes, predicted miRNAs/TFs, and underlying molecular mechanisms may be involved in atherogenesis, thus potentially contributing to the treatment and diagnosis of patients with atherosclerotic disease.

show abstract

“…Sanger sequencing was used to screen the target fragments with the correct sequence, and the screened fragments were cloned into pmirGLO vector. 29 Recombinant pmirGLO-GRIN1 vectors were used for subsequent experiments.…”

Section: Construction Of Pmirglo-grin1 (3ʹutr) Recombinant Vectorsmentioning

confidence: 99%

<p>Functional Analysis of the 3ʹ Untranslated Region of the Human <em>GRIN1</em> Gene in Regulating Gene Expression in vitro</p>

Liu

Jinghua

et al. 2020

NDT

Self Cite

View full text Add to dashboard Cite

Purpose: Abnormal expression of the NR1 subunit of the N-methyl-d-aspartate (NMDA) receptor may potentially increase the susceptibility to neuropsychiatric diseases. The purpose of this study was to investigate the functional sequence of the 3ʹUTR of the human GRIN1 gene, which encodes the GluN1 receptor to determine the effect on the expression of GluN1 receptor. Methods: We transferred seven recombinant pmirGLO recombinant vectors containing the 3ʹUTR truncated fragment of the GRIN1 gene into HEK-293, SK-N-SH, and U87 cell lines and compared the relative fluorescence intensity of adjacent length fragments. The TargetScan database was used to predict miRNAs. Then, miRNA mimics/inhibitors were co-transfected into the three cell lines with the 3ʹUTR of GRIN1 (pmirGLO-GRIN1), to investigate their influence on GRIN1 gene expression. Results: Compared with the pmirGLo-Basic vector, the relative fluorescence intensity of the complete GRIN1 gene 3ʹUTR recombinant sequence −27 bp-+1284 bp (the next base of the stop codon is +1) was significantly decreased in all three cell lines. The relative fluorescence intensities were significantly different between −27 bp-+294 bp and −27 bp-+497 bp regions, and between −27 bp-+708 bp and −27 bp-+907 bp regions. According to the prediction of the TargetScan database and analysis, miR-212-5p, miR-324-3p and miR-326 may bind to +295 bp-+497 bp, while miR-491-5p may bind to +798 bp-+907 bp. After co-transfection of miRNA mimic/inhibitor or mimic/inhibitor NC with a recombinant vector in the 3ʹUTR region of GRIN1 gene, we found that has-miR-491-5p inhibited GRIN1 expression significantly in all three cell lines, while has-miR-326 inhibitor upregulated GRIN1 expression in HEK-293 and U87 cells. Conclusion: miR-491-5p may bind to the 3ʹUTR of the GRIN1 gene (+799 bp-+805 bp, the next base of the stop codon is +1) and down-regulate gene expression in HEK-293, SK-N-SH, and U87 cell lines, which implicates a potential role of miR-491-5p in central nervous system diseases.

show abstract

hsa-miR-3177-5p and hsa-miR-3178 Inhibit 5-HT1A Expression by Binding the 3′-UTR Region in vitro

Cited by 9 publications

References 61 publications

Shared genetic links between hypothyroidism and psychiatric disorders: evidence from a comprehensive genetic analysis

Shared genetic links between hypothyroidism and psychiatric disorders: evidence from a comprehensive genetic analysis

Underlying Genes Involved in Atherosclerotic Macrophages: Insights from Microarray Data Mining

<p>Functional Analysis of the 3ʹ Untranslated Region of the Human <em>GRIN1</em> Gene in Regulating Gene Expression in vitro</p>

Contact Info

Product

Resources

About