ResearchPad - gene-expression-regulation https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Identification of crucial aberrantly methylated and differentially expressed genes related to cervical cancer using an integrated bioinformatics analysis]]> https://www.researchpad.co/article/elastic_article_13844 Methylation functions in the pathogenesis of cervical cancer. In the present study, we applied an integrated bioinformatics analysis to identify the aberrantly methylated and differentially expressed genes (DEGS), and their related pathways in cervical cancer. Data of gene expression microarrays (GSE9750) and gene methylation microarrays (GSE46306) were gained from Gene Expression Omnibus (GEO) databases. Hub genes were identified by ‘limma’ packages and Venn diagram tool. Functional analysis was conducted by FunRich. Search Tool for the Retrieval of Interacting Genes Database (STRING) was used to analyze protein–protein interaction (PPI) information. Gene Expression Profiling Interactive Analysis (GEPIA), immunohistochemistry staining, and ROC curve analysis were conducted for validation. Gene Set Enrichment Analysis (GSEA) was also performed to identify potential functions.We retrieved two upregulated-hypomethylated oncogenes and eight downregulated-hypermethylated tumor suppressor genes (TSGs) for functional analysis. Hypomethylated and highly expressed genes (Hypo-HGs) were significantly enriched in cell cycle and autophagy, and hypermethylated and lowly expressed genes (Hyper-LGs) in estrogen receptor pathway and Wnt/β-catenin signaling pathway. Estrogen receptor 1 (ESR1), Erythrocyte membrane protein band 4.1 like 3 (EPB41L3), Endothelin receptor B (EDNRB), Inhibitor of DNA binding 4 (ID4) and placenta-specific 8 (PLAC8) were hub genes. Kaplan–Meier method was used to evaluate survival data of each identified gene. Lower expression levels of ESR1 and EPB41L3 were correlated with a shorter survival time. GSEA results showed that ‘cell adhesion molecules’ was the most enriched item. This research inferred the candidate genes and pathways that might be used in the diagnosis, treatment, and prognosis of cervical cancer.

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<![CDATA[VCAM-1-targeted and PPARδ-agonist-loaded nanomicelles enhanced suppressing effects on apoptosis and migration of oxidized low-density lipoprotein-induced vascular smooth muscle cells]]> https://www.researchpad.co/article/elastic_article_13842 Purpose: Nanomicelles (NMs) have been widely used for various biomedical applications due to its unique physiochemical properties. The present study aims to investigate the effects of vascular cell adhesion molecule-1 (VCAM-1)-targeted and peroxisome proliferator-activated receptor δ (PPARδ) agonist (GW0742)-loaded NMs on apoptosis and migration in oxidized low-density lipoprotein (ox-LDL)-induced human aortic vascular smooth muscle cells (HAVSMCs).

Methods: The GW0742-loaded NMs (M-GW) and VCAM-1-targeted NMs loaded with GW0742 (TM-GW) were prepared, and then the morphologies and the size distribution of M-GM and TM-GM were observed by transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively. In vitro drug release assay of M-GM and TM-GM were performed as well. Next, HAVSMCs were cultured in medium containing ox-LDL to mimic atherosclerotic environment, and the effects of free GW0742, M-GM and TM-GM on endocytosis, cell migration and apoptosis, as well as the expression of VCAM-1, and proteins associated with migration and apoptosis were measured in HAVSMCs treated with ox-LDL.

Results: M-GM and TM-GM were successfully prepared. VCAM-1 was overexpressed in HAVSMCs treated with ox-LDL, and TM-GM had a strong targeting ability to HAVSMCs treated with ox-LDL compared with M-GM. In addition, compared with free GW0742, both M-GM and TM-GM significantly diminished cell apoptosis and migration in HAVSMCs treated with ox-LDL.

Conclusions: TM-GM had a superior suppressing effect on apoptosis and migration of ox-LDL-induced HAVSMCs.

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<![CDATA[MicroRNAs and long non-coding RNAs as novel regulators of ribosome biogenesis]]> https://www.researchpad.co/article/elastic_article_10897 Ribosome biogenesis is the fine-tuned, essential process that generates mature ribosomal subunits and ultimately enables all protein synthesis within a cell. Novel regulators of ribosome biogenesis continue to be discovered in higher eukaryotes. While many known regulatory factors are proteins or small nucleolar ribonucleoproteins, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) are emerging as a novel modulatory layer controlling ribosome production. Here, we summarize work uncovering non-coding RNAs (ncRNAs) as novel regulators of ribosome biogenesis and highlight their links to diseases of defective ribosome biogenesis. It is still unclear how many miRNAs or lncRNAs are involved in phenotypic or pathological disease outcomes caused by impaired ribosome production, as in the ribosomopathies, or by increased ribosome production, as in cancer. In time, we hypothesize that many more ncRNA regulators of ribosome biogenesis will be discovered, which will be followed by an effort to establish connections between disease pathologies and the molecular mechanisms of this additional layer of ribosome biogenesis control.

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<![CDATA[Commentary on: The potency of lncRNA MALAT1/miR-155 in altering asthmatic Th1/Th2 balance by modulation of CTLA4]]> https://www.researchpad.co/article/elastic_article_9234 Asthma is a common, allergic respiratory disorder affecting over 350 million people worldwide. One of the key features of asthma is skewing of CD4+ cells toward Th2 responses. This promotes the production of cytokines like IL-4 that induce IgE production resulting in the hypersecretion of mucus and airway smooth muscle contraction. Understanding the factors that favor Th2 expansion in asthma would provide important insights into the underlying pathogenesis of this disorder. Asthma research has focused on signaling pathways that control the transcription of key asthma-related genes. However, increasing evidence shows that post-transcriptional factors also determine CD4+ cell fate and the enhancement of allergic airway responses. A recent paper published by Liang et al. (Bioscience Reports (2020) 40, https://doi.org/10.1042/BSR20190397) highlights a novel role for the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in Th2 development in asthma. MALAT1 modulates several biological processes including alternative splicing, epigenetic modification and gene expression. It is one of the most highly expressed lncRNAs in normal tissues and MALAT1 levels correlate with poor clinical outcomes in cancer. The mechanisms of action of MALAT1 in tumor progression and metastasis remain unclear and even less is known about its effects in inflammatory disease states like asthma. The work of Liang et al. demonstrates heightened MALAT1 expression in asthma and further shows that this lncRNA targets miR-155 to promote Th2 differentiation in this disease. This insight sets the stage for future studies to examine how MALAT1 manipulation could deter allergic immune responses in asthmatic airways.

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<![CDATA[Cell Atlas technologies and insights into tissue architecture]]> https://www.researchpad.co/article/elastic_article_9194 Since Robert Hooke first described the existence of ‘cells’ in 1665, scientists have sought to identify and further characterise these fundamental units of life. While our understanding of cell location, morphology and function has expanded greatly; our understanding of cell types and states at the molecular level, and how these function within tissue architecture, is still limited. A greater understanding of our cells could revolutionise basic biology and medicine. Atlasing initiatives like the Human Cell Atlas aim to identify all cell types at the molecular level, including their physical locations, and to make this reference data openly available to the scientific community. This is made possible by a recent technology revolution: both in single-cell molecular profiling, particularly single-cell RNA sequencing, and in spatially resolved methods for assessing gene and protein expression. Here, we review available and upcoming atlasing technologies, the biological insights gained to date and the promise of this field for the future.

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<![CDATA[Bacterial phenotypic heterogeneity in DNA repair and mutagenesis]]> https://www.researchpad.co/article/elastic_article_9188 Genetically identical cells frequently exhibit striking heterogeneity in various phenotypic traits such as their morphology, growth rate, or gene expression. Such non-genetic diversity can help clonal bacterial populations overcome transient environmental challenges without compromising genome stability, while genetic change is required for long-term heritable adaptation. At the heart of the balance between genome stability and plasticity are the DNA repair pathways that shield DNA from lesions and reverse errors arising from the imperfect DNA replication machinery. In principle, phenotypic heterogeneity in the expression and activity of DNA repair pathways can modulate mutation rates in single cells and thus be a source of heritable genetic diversity, effectively reversing the genotype-to-phenotype dogma. Long-standing evidence for mutation rate heterogeneity comes from genetics experiments on cell populations, which are now complemented by direct measurements on individual living cells. These measurements are increasingly performed using fluorescence microscopy with a temporal and spatial resolution that enables localising, tracking, and counting proteins with single-molecule sensitivity. In this review, we discuss which molecular processes lead to phenotypic heterogeneity in DNA repair and consider the potential consequences on genome stability and dynamics in bacteria. We further inspect these concepts in the context of DNA damage and mutation induced by antibiotics.

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<![CDATA[The role of SUMOylation during development]]> https://www.researchpad.co/article/elastic_article_9182 During the development of multicellular organisms, transcriptional regulation plays an important role in the control of cell growth, differentiation and morphogenesis. SUMOylation is a reversible post-translational process involved in transcriptional regulation through the modification of transcription factors and through chromatin remodelling (either modifying chromatin remodelers or acting as a ‘molecular glue’ by promoting recruitment of chromatin regulators). SUMO modification results in changes in the activity, stability, interactions or localization of its substrates, which affects cellular processes such as cell cycle progression, DNA maintenance and repair or nucleocytoplasmic transport. This review focuses on the role of SUMO machinery and the modification of target proteins during embryonic development and organogenesis of animals, from invertebrates to mammals.

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<![CDATA[Small nucleolar RNAs: continuing identification of novel members and increasing diversity of their molecular mechanisms of action]]> https://www.researchpad.co/article/elastic_article_9176 Identified five decades ago amongst the most abundant cellular RNAs, small nucleolar RNAs (snoRNAs) were initially described as serving as guides for the methylation and pseudouridylation of ribosomal RNA through direct base pairing. In recent years, however, increasingly powerful high-throughput genomic approaches and strategies have led to the discovery of many new members of the family and surprising diversity in snoRNA functionality and mechanisms of action. SnoRNAs are now known to target RNAs of many biotypes for a wider range of modifications, interact with diverse binding partners, compete with other binders for functional interactions, recruit diverse players to targets and affect protein function and accessibility through direct interaction. This mini-review presents the continuing characterization of the snoRNome through the identification of new snoRNA members and the discovery of their mechanisms of action, revealing a highly versatile noncoding family playing central regulatory roles and connecting the main cellular processes.

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<![CDATA[Chloroquine and bafilomycin A mimic lysosomal storage disorders and impair mTORC1 signalling]]> https://www.researchpad.co/article/Nd1230112-cc81-4a5a-ba57-11113fa6ebb5 Autophagy is dependent upon lysosomes, which fuse with the autophagosome to complete the autophagic process and whose acidic interior permits the activity of their intraluminal degradative enzymes. Chloroquine (CQ) and bafilomycin A1 (BafA) each cause alkalinisation of the lumen and thus impair lysosomal function, although by distinct mechanisms. CQ diffuses into lysosomes and undergoes protonation, while BafA inhibits the ability of the vacuolar type H+-ATPase (v-ATPase) to transfer protons into the lysosome. In the present study, we examine the impact of CQ and BafA on the activity of mammalian target of rapamycin complex 1 (mTORC1), inhibition of which is an early step in promoting autophagy. We find each compound inhibits mTORC1 signalling, without affecting levels of protein components of the mTORC1 signalling pathway. Furthermore, these effects are not related to these agents’ capacity to inhibit autophagy or the reduction in amino acid supply from lysosomal proteolysis. Instead, our data indicate that the reduction in mTORC1 signalling appears to be due to the accumulation of lysosomal storage material. However, there are differences in responses to these agents, for instance, in their abilities to up-regulate direct targets of transcription factor EB (TFEB), a substrate of mTORC1 that drives transcription of many lysosomal and autophagy-related genes. Nonetheless, our data imply that widely used agents that alkalinise intralysosomal pH are mimetics of acute lysosomal storage disorders (LSDs) and emphasise the importance of considering the result of CQ and BafA on mTORC1 signalling when interpreting the effects of these agents on cellular physiology.

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<![CDATA[Effect of celecoxib in treatment of burn-induced hypermetabolism]]> https://www.researchpad.co/article/Ndeaf5b05-2afc-45be-92c0-1480786a5c1f Background: Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step of prostanoid biosynthesis. Under pathologic conditions, COX-2 activity can produce reactive oxygen species and toxic prostaglandin metabolites that exacerbate injury and metabolic disturbance. The present study was performed to investigate the effect of Celecoxib (the inhibitor of COX-2) treatment on lipolysis in burn mice.

Methods: One hundred male BALB/c mice were randomly divided into sham group, burn group, celecoxib group, and burn with celecoxib group (25 mice in each group). Thirty percent total body surface area (TBSA) full-thickness injury was made for mice to mimic burn injuries. Volume of oxygen uptake (VO2), volume of carbon dioxide output (VCO2), respiratory exchange ratio (RER), energy expenditure (EE), COX-2 and uncoupled protein-1 (UCP-1) expression in brown adipose tissue (BAT) were measured for different groups.

Results: Adipose tissue (AT) activation was associated with the augmentation of mitochondria biogenesis, and UCP-1 expression in isolated iBAT mitochondria. In addition, VO2, VCO2, EE, COX-2, and UCP-1 expression were significantly higher in burn group than in burn with celecoxib group (P<0.05).

Conclusion: BAT plays important roles in burn injury-induced hypermetabolism through its morphological changes and elevating the expression of UCP-1. Celecoxib could improve lipolysis after burn injury.

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<![CDATA[Comprehensive analysis of PPARγ agonist activities of stereo-, regio-, and enantio-isomers of hydroxyoctadecadienoic acids]]> https://www.researchpad.co/article/Ncba0b326-176f-4db2-bf87-2a3eba460f56 Hydroxyoctadecadienoic acids (HODEs) are produced by oxidation and reduction of linoleates. There are several regio- and stereo-isomers of HODE, and their concentrations in vivo are higher than those of other lipids. Although conformational isomers may have different biological activities, comparative analysis of intracellular function of HODE isomers has not yet been performed. We evaluated the transcriptional activity of peroxisome proliferator-activated receptor γ (PPARγ), a therapeutic target for diabetes, and analyzed PPARγ agonist activity of HODE isomers. The lowest scores for docking poses of 12 types of HODE isomers (9-, 10-, 12-, and 13-HODEs) were almost similar in docking simulation of HODEs into PPARγ ligand-binding domain (LBD). Direct binding of HODE isomers to PPARγ LBD was determined by water-ligand observed via gradient spectroscopy (WaterLOGSY) NMR experiments. In contrast, there were differences in PPARγ agonist activities among 9- and 13-HODE stereo-isomers and 12- and 13-HODE enantio-isomers in a dual-luciferase reporter assay. Interestingly, the activity of 9-HODEs was less than that of other regio-isomers, and 9-(E,E)-HODE tended to decrease PPARγ-target gene expression during the maturation of 3T3-L1 cells. In addition, 10- and 12-(Z,E)-HODEs, which we previously proposed as biomarkers for early-stage diabetes, exerted PPARγ agonist activity. These results indicate that all HODE isomers have PPARγ-binding affinity; however, they have different PPARγ agonist activity. Our findings may help to understand the biological function of lipid peroxidation products.

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<![CDATA[MEHP interferes with mitochondrial functions and homeostasis in skeletal muscle cells]]> https://www.researchpad.co/article/Na411c472-0723-403f-89af-3381276a1e18

Abstract

Di (2-ethylhexyl) phthalate (DEHP) is a plasticizer frequently leached out from polyvinyl chloride (PVC) products and is quickly metabolized to its monoester equivalent mono(2-ethylhexyl) phthalate (MEHP) once enters organisms. Exposure to DEHP/MEHP through food chain intake has been shown to modified metabolism but its effect on the development of metabolic myopathy of skeletal muscle (SKM) has not been revealed so far. Here, we found that MEHP repressed myogenic terminal differentiation of proliferating myoblasts (PMB) and confluent myoblasts (CMB) but had weak effect on this process once it had been initiated. The transition of mitochondria (MITO) morphology from high efficient filamentary network to low efficient vesicles was triggered by MEHP, implying its negative effects on MITO functions. The impaired MITO functions was further demonstrated by reduced MITO DNA (mtDNA) level and SDH enzyme activity as well as highly increased reactive oxygen species (ROS) in cells after MEHP treatment. The expression of metabolic genes, including PDK4, CPT1b, UCP2, and HO1, was highly increased by MEHP and the promoters of PDK4 and CPT1b were also activated by MEHP. Additionally, the stability of some subunits in the oxidative phosphorylation system (OXPHOS) complexes was found to be reduced by MEHP, implying defective oxidative metabolism in MITO and which was confirmed by repressed palmitic acid oxidation in MEHP-treated cells. Besides, MEHP also blocked insulin-induced glucose uptake. Taken together, our results suggest that MEHP is inhibitory to myogenesis and is harmful to MITO functions in SKM, so its exposure should be avoided or limited.

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<![CDATA[Extracellular DNA in blood products and its potential effects on transfusion]]> https://www.researchpad.co/article/N2c43a6d9-b325-4827-8d79-69a6ffb5c163

Abstract

Blood transfusions are sometimes necessary after a high loss of blood due to injury or surgery. Some people need regular transfusions due to medical conditions such as haemophilia or cancer. Studies have suggested that extracellular DNA including mitochondrial DNA present in the extracellular milieu of transfused blood products has biological actions that are capable of activating the innate immune systems and potentially contribute to some adverse reactions in transfusion. From the present work, it becomes increasingly clear that extracellular DNA encompassed mitochondrial DNA is far from being biologically inert in blood products. It has been demonstrated to be present in eligible blood products and thus can be transfused to blood recipients. Although the presence of extracellular DNA in human plasma was initially detected in 1948, some aspects have not been fully elucidated. In this review, we summarize the potential origins, clearance mechanisms, relevant structures, and potential role of extracellular DNA in the innate immune responses and its relationship with individual adverse reactions in transfusion.

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<![CDATA[Differential regulation of sFlt-1 splicing by U2AF65 and JMJD6 in placental-derived and endothelial cells]]> https://www.researchpad.co/article/N36b40f8f-24a9-4d5b-a798-7b60fc5e429d

Abstract

Despite years of study, the gestational disorder preeclampsia (PE) remains poorly understood. One proposed mechanism of PE development is increased soluble VEGF receptor-1 (sFlt-1), ultimately causing angiogenic imbalance and endothelial dysfunction. The soluble protein is an alternative splice variant of FLT1, which also encodes for the full-length receptor Flt-1. The mechanism of the alternative splicing, and the reason for its inappropriate increase in preeclampsia, is not well understood. U2 auxiliary factor 65 (U2AF65) and jumonji C domain-containing protein 6 (JMJD6) have been implicated in the splicing of sFlt-1. Using siRNA knockdown and plasmid overexpression in immortalized placental trophoblasts (BeWo) and primary endothelial cells (HUVECs), we examined the role these proteins play in production of sFlt-1. Our results showed that U2AF65 has little, if any, effect on sFlt-1 splicing, and JMJD6 may enhance sFlt-1 splicing, but is not necessary for splicing to occur. Utilizing a hypoxic environment to mimic conditions of the preeclamptic placenta, as well as examining placentae in the reduced uterine perfusion pressure (RUPP) model of PE, which exhibits increased circulating sFlt-1, we found increased expression of JMJD6 in both hypoxic cells and placental tissue. Additionally, we observed a potential role for U2AF65 and JMJD6 to regulate the extracellular matrix enzyme heparanase, which may be involved in the release of sFlt-1 protein from the extracellular matrix. It will be important to study the role of these proteins in different tissues in the future, as changes in expression had differential effects on sFlt-1 splicing in the different cell types studied here.

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<![CDATA[Effect of lentivirus-mediated CFTR overexpression on oxidative stress injury and inflammatory response in the lung tissue of COPD mouse model]]> https://www.researchpad.co/article/N60e4f002-1184-495a-89f8-252a9d63c534

Abstract

We aimed to investigate the regulatory mechanism of lentivirus-mediated overexpression of cystic fibrosis transmembrane conductance regulator (CFTR) in oxidative stress injury and inflammatory response in the lung tissue of mouse model of chronic obstructive pulmonary disease (COPD). COPD mouse model induced by cigarette smoke was established and normal mice were used as control. The mice were assigned into a normal group (control), a model group (untreated), an oe-CFTR group (injection of lentivirus overexpressing CFTR), and an oe-NC group (negative control, injection of lentivirus expressing irrelevant sequences). Compared with the oe-NC group, the oe-CFTR group had higher CFTR expression and a better recovery of pulmonary function. CFTR overexpression could inhibit the pulmonary endothelial cell apoptosis, reduce the levels of glutathione (GSH), reactive oxygen species (ROS), and malondialdehyde (MDA) and increase the values of superoxide dismutase (SOD), GSH peroxidase (GSH-Px), and total antioxidant capacity (T-AOC). The overexpression also led to reductions in the white blood cell (WBC) count in alveolus pulmonis, the concentrations of C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor-α, and the protein expressions of NF-κB p65, ERK, JNK, p-EPK, and p-JNK related to MAPK/NF-κB p65 signaling pathway. In conclusion, CFTR overexpression can protect lung tissues from injuries caused by oxidative stress and inflammatory response in COPD mouse model. The mechanism behind this may be related to the suppression of MAPK/NF-κB p65 signaling pathway.

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<![CDATA[Nascent SecM chain interacts with outer ribosomal surface to stabilize translation arrest]]> https://www.researchpad.co/article/N037e1cb1-b1b1-41d5-b26b-df1652b94ad4

SecM, a bacterial secretion monitor protein, posttranscriptionally regulates downstream gene expression via translation elongation arrest. SecM contains a characteristic amino acid sequence called the arrest sequence at its C-terminus, and this sequence acts within the ribosomal exit tunnel to stop translation. It has been widely assumed that the arrest sequence within the ribosome tunnel is sufficient for translation arrest. We have previously shown that the nascent SecM chain outside the ribosomal exit tunnel stabilizes translation arrest, but the molecular mechanism is unknown. In this study, we found that residues 57–98 of the nascent SecM chain are responsible for stabilizing translation arrest. We performed alanine/serine-scanning mutagenesis of residues 57–98 to identify D79, Y80, W81, H84, R87, I90, R91, and F95 as the key residues responsible for stabilization. The residues were predicted to be located on and near an α-helix-forming segment. A striking feature of the α-helix is the presence of an arginine patch, which interacts with the negatively charged ribosomal surface. A photocross-linking experiment showed that Y80 is adjacent to the ribosomal protein L23, which is located next to the ribosomal exit tunnel when translation is arrested. Thus, the folded nascent SecM chain that emerges from the ribosome exit tunnel interacts with the outer surface of the ribosome to stabilize translation arrest.

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<![CDATA[Translation elongation factor 1A2 is encoded by one of four closely related eef1a genes and is dispensable for survival in zebrafish]]> https://www.researchpad.co/article/Nac80981c-06d4-4c6e-ace4-3d6fb243bde1

Abstract

Zebrafish are valuable model organisms for the study of human single-gene disorders: they are genetically manipulable, their development is well understood, and mutant lines with measurable, disease-appropriate phenotypic abnormalities can be used for high throughput drug screening approaches. However, gene duplication events in zebrafish can result in redundancy of gene function, masking loss-of-function phenotypes and thus confounding this approach to disease modelling. Furthermore, recent studies have yielded contrasting results depending on whether specific genes are targeted using genome editing to make mutant lines, or whether morpholinos are used (morphants). De novo missense mutations in the human gene EEF1A2, encoding a tissue-specific translation elongation factor, cause severe neurodevelopmental disorders; there is a real need for a model system to study these disorders and we wanted to explore the possibility of a zebrafish model. We identified four eef1a genes and examined their developmental and tissue-specific expression patterns: eef1a1l1 is first to be expressed while eef1a2 is only detected later during development. We then determined the effects of introducing null mutations into translation elongation factor 1A2 (eEF1A2) in zebrafish using CRISPR/Cas9 gene editing, in order to compare the results with previously described morphants, and with severe neurodegenerative lethal phenotype of eEF1A2-null mice. In contrast with both earlier analyses in zebrafish using morpholinos and with the mouse eEF1A2-null mice, disruption of the eef1a2 gene in zebrafish is compatible with normal lifespan. The resulting lines, however, may provide a valuable platform for studying the effects of expression of mutant human eEF1A2 mRNA.

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<![CDATA[Interplay of mRNA capping and transcription machineries]]> https://www.researchpad.co/article/N18a036eb-6971-4a72-8ad3-b564ca06e6ed

Abstract

Early stages of transcription from eukaryotic promoters include two principal events: the capping of newly synthesized mRNA and the transition of RNA polymerase II from the preinitiation complex to the productive elongation state. The capping checkpoint model implies that these events are tightly coupled, which is necessary for ensuring the proper capping of newly synthesized mRNA. Recent findings also show that the capping machinery has a wider effect on transcription and the entire gene expression process. The molecular basis of these phenomena is discussed.

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<![CDATA[Integrated analysis of DNA methylation and mRNA expression profiles to identify key genes in head and neck squamous cell carcinoma]]> https://www.researchpad.co/article/N273f7cc1-c4d9-4b7b-9351-3710564f17a2

Abstract

DNA methylation has been demonstrated to play significant roles in the etiology and pathogenesis of head and neck squamous cell carcinoma (HNSCC). In the present study, methylation microarray dataset (GSE87053) and gene expression microarray dataset (GSE23558) were downloaded from GEO database and analyzed through R language. A total of 255 hypermethylated-downregulated genes and 114 hypomethylated-upregulated genes were finally identified. Functional enrichment analyses were performed and a comprehensive protein–protein interaction (PPI) network was constructed. Subsequently, the top ten hub genes selected by Cytoscape software were subjected to further analyses. It was illustrated that the expression level of CSF2, CTLA4, ETS1, PIK3CD, and CFTR was intimately associated with HNSCC. Survival analysis suggested that CTLA4 and FGFR2 could serve as effective independent prognostic biomarkers for HNSCC patients. Overall, our study lay a groundwork for further investigation into the underlying molecular mechanisms in HNSCC carcinogenesis, providing potential biomarkers and therapeutic targets for HNSCC.

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<![CDATA[The protective role of MiR-206 in regulating cardiomyocytes apoptosis induced by ischemic injury by targeting PTP1B]]> https://www.researchpad.co/article/N2a5c1300-bdae-4ae7-9168-9f3c7ead11a6

Abstract

MicroRNAs play essential roles in the regulation and pathophysiology of acute myocardial infarction (AMI). The purpose of the present study was to assess the expression signature of miR-206 in rat heart with AMI and the corresponding molecular mechanism. The expression of miR-206 significantly decreased in the infarcted myocardial areas and in hypoxia-induced cardiomyocytes, compared with that in the noninfarcted areas. Overexpression of miR-206 decreased cardiomyocytes apoptosis and the down-regulation of miR-206 increased cardiomyocytes apoptosis in vitro. In addition, overexpression of miR-206 in rat heart in vivo remarkably reduced myocardial infarct size and cardiomyocytes apoptosis. We identified that miR-206 had a protective effect on cardiomyocytes apoptosis with the association of its target protein tyrosine phosphatase 1B (PTP1B). Gain-of-function of miR-206 inhibited PTP1B expression and loss-of-function of miR-206 up-regulated PTP1B expression. Furthermore, overexpression of PTP1B significantly increased cardiomyocytes apoptosis. These results together suggest the protective effect of miR-206 against cardiomyocytes apoptosis induced by AMI by targeting PTP1B.

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