Coexpression Network Analysis of miRNA-142 Overexpression in Neuronal Cells

MicroRNAs are small noncoding RNA molecules, which are differentially expressed in diverse biological processes and are also involved in the regulation of multiple genes. A number of sites in the 3′ untranslated regions (UTRs) of different mRNAs allow complimentary binding for a microRNA, leading to their posttranscriptional regulation. The miRNA-142 is one of the microRNAs overexpressed in neurons that is found to regulateSIRT1andMAOAgenes. Differential analysis of gene expression data, which is focused on identifying up- or downregulated genes, ignores many relationships between genes affected by miRNA-142 overexpression in a cell. Thus, we applied a correlation network model to identify the coexpressed genes and to study the impact of miRNA-142 overexpression on this network. Combining multiple sources of knowledge is useful to infer meaningful relationships in systems biology. We applied coexpression model on the data obtained from wild type and miR-142 overexpression neuronal cells and integrated miRNA seed sequence mapping information to identify genes greatly affected by this overexpression. Larger differences in the enriched networks revealed that the nervous system development related genes such asTEAD2, PLEKHA6, andPOGLUT1were greatly impacted due to miRNA-142 overexpression.

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Exogenous Neonatal Erythropoietin Mitigates Brain Damage After a Combination of Prenatal Hypoxic-Ischemia and Lipopolysaccharide Inflammation in Rats

Journal of Neurosurgery Pediatrics ◽

10.3171/ped/2008/1/4/paper9 ◽

2008 ◽

Vol 1 (4) ◽

pp. A353

Author(s):

Shenandoah Robinson ◽

Qing Li

Keyword(s):

Brain Damage ◽

Intracellular Signaling ◽

System Development ◽

Intrauterine Infection ◽

Artery Occlusion ◽

Nervous System Development ◽

Human Infants ◽

Hypoxic Ischemia ◽

Show Evidence ◽

The Impact

Introduction Many infants born very preterm who suffer brain damage most likely experienced a combined insult from intrauterine infection and placental insufficiency. Damage is thought to be synergistic rather than additive but the mechanisms of combined injury remain elusive. A combination of lipopolysaccharide-induced inflammation and hypoxia-ischemia has been used in rats to model the dual insult that occurs in human infants prenatally. Erythropoietin, a pleiotrophic cytokine that is essential for central nervous system development, ameliorates brain injury after isolated hypoxic-ischemic or inflammatory insults through different intracellular signaling pathways. We hypothesized that exogenous neonatal EPO administration would lessen the damage of a combined prenatal insult in rats. Methods On embryonic Day 18 fetal rats experienced 60 minutes of transient uterine artery occlusion with or without intracervical LPS administration with sham controls receiving surgery but no occlusion and saline for LPS. Survival was recorded and histological biochemical and functional assays were performed. Means were compared with ANOVA with Tukey HSD post hoc analysis. Results After a combined insult of HI and 0.15-mg/kg LPS on E18 the survival of pups by postnatal Day 1 (P1) decreased from 77% with HI alone to 22% for LPS plus HI. When exogenous systemic EPO was administered P1–P3 survival to P9 improved markedly from 40% (2 of 5) for saline-treated insult pups to 100% (6 of 6) for EPO-treated. Initial histological analyses show EPO decreases the number of brain activated caspase 3 and activated microglia by P9. Additional analyses will be presented. Conclusion As at least 60% of placentas from infants born pre-term show evidence of chorioamnionitis, assessment of the impact of exogenous EPO on a model of a combination injury is essential prior to proceeding with a clinical trial. Initial results indicate neonatal exogenous EPO mitigates damage from the combined insult.

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Neurotrophins as Key Regulators of Cell Metabolism: Implications for Cholesterol Homeostasis

International Journal of Molecular Sciences ◽

10.3390/ijms22115692 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5692

Author(s):

Mayra Colardo ◽

Noemi Martella ◽

Daniele Pensabene ◽

Silvia Siteni ◽

Sabrina Di Bartolomeo ◽

...

Keyword(s):

Growth Factors ◽

Cholesterol Metabolism ◽

System Development ◽

Cell Metabolism ◽

Redox Balance ◽

Nervous System Development ◽

Cholesterol Homeostasis ◽

Signaling Cascades ◽

Target Cells ◽

The Impact

Neurotrophins constitute a family of growth factors initially characterized as predominant mediators of nervous system development, neuronal survival, regeneration and plasticity. Their biological activity is promoted by the binding of two different types of receptors, leading to the generation of multiple and variegated signaling cascades in the target cells. Increasing evidence indicates that neurotrophins are also emerging as crucial regulators of metabolic processes in both neuronal and non-neuronal cells. In this context, it has been reported that neurotrophins affect redox balance, autophagy, glucose homeostasis and energy expenditure. Additionally, the trophic support provided by these secreted factors may involve the regulation of cholesterol metabolism. In this review, we examine the neurotrophins’ signaling pathways and their effects on metabolism by critically discussing the most up-to-date information. In particular, we gather experimental evidence demonstrating the impact of these growth factors on cholesterol metabolism.

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MicroRNAs in domestic livestock

Physiological Genomics ◽

10.1152/physiolgenomics.00009.2013 ◽

2013 ◽

Vol 45 (16) ◽

pp. 685-696 ◽

Cited By ~ 16

Author(s):

Attia Fatima ◽

Dermot G. Morris

Keyword(s):

Posttranscriptional Regulation ◽

Noncoding Rna ◽

Expression Patterns ◽

Regulation Of Gene Expression ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Small Noncoding Rna ◽

Domestic Livestock ◽

Temporal Expression Pattern ◽

Mrna Binding

microRNAs (miRNAs) are a class of small noncoding RNA that bind to complementary sequences in the untranslated regions of multiple target mRNAs resulting in posttranscriptional regulation of gene expression. The recent discovery and expression-profiling studies of miRNAs in domestic livestock have revealed both their tissue-specific and temporal expression pattern. In addition, breed-dependent expression patterns as well as single nucleotide polymorphisms in either the miRNA or in the target mRNA binding site have revealed associations with traits of economic importance and highlight the potential use of miRNAs in future genomic selection programs.

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microRNA: The Impact on Cancer Stemness and Therapeutic Resistance

Cells ◽

10.3390/cells9010008 ◽

2019 ◽

Vol 9 (1) ◽

pp. 8 ◽

Cited By ~ 6

Author(s):

Xueqiao Jiao ◽

Xianling Qian ◽

Longyuan Wu ◽

Bo Li ◽

Yi Wang ◽

...

Keyword(s):

Stem Cells ◽

Noncoding Rna ◽

Tumor Recurrence ◽

Tumor Promoter ◽

Therapeutic Resistance ◽

Cancer Therapies ◽

Cancer Treatments ◽

Small Noncoding Rna ◽

Anti Cancer ◽

The Impact

Cancer ranks as the second leading cause of death worldwide, causing a large social and economic burden. However, most anti-cancer treatments face the problems of tumor recurrence and metastasis. Therefore, finding an effective cure for cancer needs to be solved urgently. Recently, the discovery of cancer stem cells (CSCs) provides a new orientation for cancer research and therapy. CSCs share main characteristics with stem cells and are able to generate an entire tumor. Besides, CSCs usually escape from current anti-cancer therapies, which is partly responsible for tumor recurrence and poor prognosis. microRNAs (miRNAs) belong to small noncoding RNA and regulate gene post-transcriptional expression. The dysregulation of miRNAs leads to plenty of diseases, including cancer. The aberrant miRNA expression in CSCs enhances stemness maintenance. In this review, we summarize the role of miRNAs on CSCs in the eight most common cancers, hoping to bridge the research of miRNAs and CSCs with clinical applications. We found that miRNAs can act as tumor promoter or suppressor. The dysregulation of miRNAs enhances cell stemness and contributes to tumor metastasis and therapeutic resistance via the formation of feedback loops and constitutive activation of carcinogenic signaling pathways. More importantly, some miRNAs may be potential targets for diagnosis, prognosis, and cancer treatments.

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Human microRNAs in host–parasite interaction: a review

3 Biotech ◽

10.1007/s13205-020-02498-6 ◽

2020 ◽

Vol 10 (12) ◽

Author(s):

Sujay Paul ◽

Luis M. Ruiz-Manriquez ◽

Francisco I. Serrano-Cano ◽

Carolina Estrada-Meza ◽

Karla A. Solorio-Diaz ◽

...

Keyword(s):

Noncoding Rna ◽

Fine Tuning ◽

Transcriptional Level ◽

Response Modulation ◽

Rna Molecules ◽

Small Noncoding Rna ◽

Diagnosis And Prognosis ◽

Cell Proliferation And Differentiation ◽

Host Parasite ◽

The Impact

AbstractMicroRNAs (miRNAs) are a group of small noncoding RNA molecules with significant capacity to regulate the gene expression at the post-transcriptional level in a sequence-specific manner either through translation repression or mRNA degradation triggering a fine-tuning biological impact. They have been implicated in several processes, including cell growth and development, signal transduction, cell proliferation and differentiation, metabolism, apoptosis, inflammation, and immune response modulation. However, over the last few years, extensive studies have shown the relevance of miRNAs in human pathophysiology. Common human parasitic diseases, such as Malaria, Leishmaniasis, Amoebiasis, Chagas disease, Schistosomiasis, Toxoplasmosis, Cryptosporidiosis, Clonorchiasis, and Echinococcosis are the leading cause of death worldwide. Thus, identifying and characterizing parasite-specific miRNAs and their host targets, as well as host-related miRNAs, are important for a deeper understanding of the pathophysiology of parasite-specific diseases at the molecular level. In this review, we have demonstrated the impact of human microRNAs during host−parasite interaction as well as their potential to be used for diagnosis and prognosis purposes.

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The RNA Chaperone Hfq Is Required for Virulence of Bordetella pertussis

Infection and Immunity ◽

10.1128/iai.00345-13 ◽

2013 ◽

Vol 81 (11) ◽

pp. 4081-4090 ◽

Cited By ~ 27

Author(s):

Ilona Bibova ◽

Karolina Skopova ◽

Jiri Masin ◽

Ondrej Cerny ◽

David Hot ◽

...

Keyword(s):

Bordetella Pertussis ◽

Posttranscriptional Regulation ◽

Noncoding Rna ◽

Whooping Cough ◽

Lethal Dose ◽

Rna Chaperone ◽

Content Type ◽

Small Noncoding Rna ◽

Mrna Targets

ABSTRACTBordetella pertussisis a Gram-negative pathogen causing the human respiratory disease called pertussis or whooping cough. Here we examined the role of the RNA chaperone Hfq inB. pertussisvirulence. Hfq mediates interactions between small regulatory RNAs and their mRNA targets and thus plays an important role in posttranscriptional regulation of many cellular processes in bacteria, including production of virulence factors. We characterized anhfqdeletion mutant (Δhfq) ofB. pertussis18323 and show that the Δhfqstrain produces decreased amounts of the adenylate cyclase toxin that plays a central role inB. pertussisvirulence. Production of pertussis toxin and filamentous hemagglutinin was affected to a lesser extent.In vitro, the ability of the Δhfqstrain to survive within macrophages was significantly reduced compared to that of the wild-type (wt) strain. The virulence of the Δhfqstrain in the mouse respiratory model of infection was attenuated, with its capacity to colonize mouse lungs being strongly reduced and its 50% lethal dose value being increased by one order of magnitude over that of the wt strain. In mixed-infection experiments, the Δhfqstrain was then clearly outcompeted by the wt strain. This requirement for Hfq suggests involvement of small noncoding RNA regulation inB. pertussisvirulence.

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Role of Nuclear Receptors in Central Nervous System Development and Associated Diseases

Journal of Experimental Neuroscience ◽

10.4137/jen.s25480 ◽

2015 ◽

Vol 9s2 ◽

pp. JEN.S25480 ◽

Cited By ~ 8

Author(s):

Ana Ana Maria ◽

Moreno-Ramos Oscar Andréas ◽

Neena B. Haider

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Nuclear Receptors ◽

System Development ◽

Nuclear Hormone Receptor ◽

Nervous System Development ◽

Wide Range ◽

And Function ◽

The Impact

The nuclear hormone receptor (NHR) superfamily is composed of a wide range of receptors involved in a myriad of important biological processes, including development, growth, metabolism, and maintenance. Regulation of such wide variety of functions requires a complex system of gene regulation that includes interaction with transcription factors, chromatin-modifying complex, and the proper recognition of ligands. NHRs are able to coordinate the expression of genes in numerous pathways simultaneously. This review focuses on the role of nuclear receptors in the central nervous system and, in particular, their role in regulating the proper development and function of the brain and the eye. In addition, the review highlights the impact of mutations in NHRs on a spectrum of human diseases from autism to retinal degeneration.

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Pre- and peri-implantation Zika virus infection impairs fetal development by targeting trophectoderm cells

Nature Communications ◽

10.1038/s41467-019-12063-2 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 7

Author(s):

Lei Tan ◽

Lauretta A. Lacko ◽

Ting Zhou ◽

Delia Tomoiaga ◽

Romulo Hurtado ◽

...

Keyword(s):

Zika Virus ◽

System Development ◽

Neural Progenitor Cell ◽

Nervous System Development ◽

Zikv Infection ◽

Neural Lineage ◽

Trophectoderm Cells ◽

Increased Risk ◽

Underlying Mechanisms ◽

The Impact

Abstract Zika virus (ZIKV) infection results in an increased risk of spontaneous abortion and poor intrauterine growth although the underlying mechanisms remain undetermined. Little is known about the impact of ZIKV infection during the earliest stages of pregnancy, at pre- and peri-implantation, because most current ZIKV pregnancy studies have focused on post-implantation stages. Here, we demonstrate that trophectoderm cells of pre-implantation human and mouse embryos can be infected with ZIKV, and propagate virus causing neural progenitor cell death. These findings are corroborated by the dose-dependent nature of ZIKV susceptibility of hESC-derived trophectoderm cells. Single blastocyst RNA-seq reveals key transcriptional changes upon ZIKV infection, including nervous system development, prior to commitment to the neural lineage. The pregnancy rate of mice is >50% lower in pre-implantation infection than infection at E4.5, demonstrating that pre-implantation ZIKV infection leads to miscarriage. Cumulatively, these data elucidate a previously unappreciated association of pre- and peri-implantation ZIKV infection and microcephaly.

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Mouse Cytomegalovirus MicroRNAs Dominate the Cellular Small RNA Profile during Lytic Infection and Show Features of Posttranscriptional Regulation

Journal of Virology ◽

10.1128/jvi.01313-07 ◽

2007 ◽

Vol 81 (24) ◽

pp. 13771-13782 ◽

Cited By ~ 73

Author(s):

Lars Dölken ◽

Jonathan Perot ◽

Valérie Cognat ◽

Abdelmalek Alioua ◽

Matthias John ◽

...

Keyword(s):

Gene Expression ◽

Posttranscriptional Regulation ◽

Noncoding Rna ◽

Murine Cytomegalovirus ◽

Knockout Mutant ◽

Double Knockout ◽

Viral Mirnas ◽

Small Noncoding Rna ◽

Human Cmv

ABSTRACT MicroRNAs (miRNAs) are small, noncoding RNA molecules that regulate gene expression at the posttranscriptional level. Originally identified in a variety of organisms ranging from plants to mammals, miRNAs have recently been identified in several viruses. Viral miRNAs may play a role in modulating both viral and host gene expression. Here, we report on the identification and characterization of 18 viral miRNAs from mouse fibroblasts lytically infected with the murine cytomegalovirus (MCMV). The MCMV miRNAs are expressed at early times of infection and are scattered in small clusters throughout the genome with up to four distinct miRNAs processed from a single transcript. No significant homologies to human CMV-encoded miRNAs were found. Remarkably, as soon as 24 h after infection, MCMV miRNAs constituted about 35% of the total miRNA pool, and at 72 h postinfection, this proportion was increased to more than 60%. However, despite the abundance of viral miRNAs during the early phase of infection, the expression of some MCMV miRNAs appeared to be regulated. Hence, for three miRNAs we observed polyuridylation of their 3′ end, coupled to subsequent degradation. Individual knockout mutants of two of the most abundant MCMV miRNAs, miR-m01-4 and miR-M44-1, or a double knockout mutant of miR-m21-1 and miR-M23-2, incurred no or only a very mild growth deficit in murine embryonic fibroblasts in vitro.

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A detailed observational study of maternal and neonatal variables affecting the thyroid-stimulating hormone levels in neonates

Egyptian Pediatric Association Gazette ◽

10.1186/s43054-021-00080-0 ◽

2021 ◽

Vol 69 (1) ◽

Author(s):

N. R. Verma ◽

G. Naik ◽

S. Patel ◽

P. Padhi ◽

T. Naik ◽

...

Keyword(s):

Birth Weight ◽

Negative Correlation ◽

Screening Program ◽

System Development ◽

Perinatal Period ◽

Maternal Blood ◽

Thyroid Stimulating Hormone ◽

Nervous System Development ◽

The Impact ◽

Stimulating Hormone

Abstract Background Thyroid hormones are essential for fetal growth and the central nervous system development. Thyroid-stimulating hormone (TSH) is the key regulatory hormone. Their levels are quite dynamic in the perinatal period and are influenced by multiple factors. These factors should be taken into consideration during newborn screening. This study aimed to observe the impact of maternal and neonatal factors on neonatal TSH status. Results Neonatal TSH (nTSH) depicted a positive correlation with parity (p = 0.066) while negative correlation recorded with maternal blood haemoglobin (p = 0.007) among maternal factors. New-born length (p = 0.027) and birth weight (p < 0.001) exhibited a negative correlation with nTSH among neonatal factors. Conclusions This study concludes that among all the maternal and neonatal factors, birth weight shows the most influence on nTSH. However, the effect may be compounded by other factors. As these risk elements rarely occur singly, it is often difficult to find the exposure which confer the risk on children. These factors should be considered while interpreting the result of the screening program.

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