scholarly journals Modulation of ADARs mRNA expression in congenital heart defect patients

2018 ◽  
Author(s):  
Faiza Altaf ◽  
Cornelia Vesely ◽  
Abdul Malik Sheikh ◽  
Rubab Munir ◽  
Syed Tahir Abbass Shah ◽  
...  
Keyword(s):  
Rna Editing ◽  
Heart Development ◽  
Congenital Heart ◽  
Heart Tissue ◽  
Vital Role ◽  
Expression Change ◽  
Aberrant Expression ◽  
Protein Coding ◽  
Cardiovascular Defects

AbstractAdenosine (A) to inosine (I) RNA editing, is a hydrolytic deamination reaction catalyzed by adenosine deaminase (ADAR) acting on RNA enzymes. RNA editing is a molecular process that involves the post-transcriptional modification of RNA transcripts. Interestingly, few studies have been carried out to determine the role of RNA editing in vascular disease. The current study found that in blood samples positive for congenital heart disease (CHD) ADAR1 and ADAR2 expression change at RNA level was opposite to each other. That is, an increase of ADAR1 mRNA was noticed in human CHD cases, whereas ADAR2 mRNA was vastly down-regulated. The increase in ADAR1 may be explained by the stress induced by CHD. The dramatic decrease in ADAR2 in CHD cases was unexpected and prompted further investigation into its effects on the heart. Therefore we performed expression analysis on a microarray data encompassing ischemic and non-Ischemic cardiomyopathy patient myocardial tissues. A strong down-regulation of ADAR2 was observed in both ischemic and especially non-ischemic cases. However, ADAR1 showed a mild increase in the case of non-ischemic myocardial tissues. To further explore the role of ADAR2 with respect to heart physiology. We selected a protein coding gene filamin B (FLNB). FLNB is known to play an important role in heart development. Although there were no observable changes in its expression, the editing levels of FLNB dropped dramatically in ADAR2-/- mice. We also performed miRNA profiling from ADAR2 -/- mice heart tissue revealed a decrease in expression of miRNAs. It is established that aberrant expression of these miRNAs is often associated with cardiac defects. This study proposes that sufficient amounts of ADAR2 might play a vital role in preventing cardiovascular defects.

Hox and Tale transcription factors in heart development and disease

2018 ◽  
Vol 62 (11-12) ◽  
pp. 837-846 ◽  
Author(s):  
Fabienne Lescroart ◽  
Stephane Zaffran
Keyword(s):  
Transcription Factors ◽  
Congenital Heart Defects ◽  
Heart Development ◽  
Congenital Heart ◽  
Hox Genes ◽  
Heart Defects ◽  
First Year ◽  
First Year Of Life ◽  
Cardiac Mesoderm

Hox genes are highly conserved transcription factors with critical functions during development, in particular for patterning the antero-posterior axis of the embryo. Their action is very often associated with cofactors including the TALE family transcription factors. From Drosophila to vertebrates, Hox genes have been shown to have a major role in heart development. In this review, we focus on the increasing evidence implicating the anterior Hox genes and the Tale family members during heart development both in the cardiac mesoderm and in neural crest cells. Congenital heart defects are the leading cause of death in the first year of life and a better understanding of the role of Hox and Tale factors is highly relevant to human pathologies and will provide novel mechanistic insights into the underlying defects.

The effect of nutri-epigenomic agent “pterostilbene” on the expression of ADAR enzyme(s) in HCC animal model

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Islam A Desoky ◽  
Kamelia Ahmed Zaki ◽  
Magda I Mohamad ◽  
Samar Kamal Kassim
Keyword(s):  
Serum Albumin ◽  
Rna Editing ◽  
Conflicts Of Interest ◽  
Potential Effect ◽  
Vital Role ◽  
Male Rats ◽  
Control Group ◽  
Aberrant Expression ◽  
Dynamic Landscape ◽  
Aberrant Rna

Abstract Background A-to-I RNA editing represents a new player in the pathogenesis of cancer. However, the knowledge of RNA editing process in cancer is still limited and represents only the tip of the iceberg. The ADAR gene family regulate the dynamic landscape of RNA editing. Aberrant RNA editing status played a vital role in the pathogenesis of hepatocellular carcinoma (HCC). The nutri-epigenomic agent- pterostilbene- exhibits anti-inflammatory, antioxidative and antiproliferative activities. However, the effect of pterostilbene on ADAR(s) expression in HCC was not studied before. Aim of the work to evaluate the potential effect of pterostilbene administration on Adar(s) expression in HCC rats. Materials and methods Twenty four adult male rats were randomly divided into 4 groups: the control group, untreated HCC group received diethylnitrosamine (DENA) for 14 weeks, HCC group take received pterostilbene and DENA for 14 weeks, and non-HCC rats were given pterostilbene for 14 weeks. These groups were subjected to histological examination of liver tissues, laboratory measures (serum albumin, ALT, AST, and α fetoprotein), and Adar(s) expression by real time-PCR. Results liver enzymes (ALT, AST) and α fetoprotein levels in treated HCC group were significantly lower than untreated HCC group (p<0.05). Serum albumin levels were significantly higher in treated HCC rats than untreated HCC group (P<0.05). Adar1 was highly expressed in untreated HCC rats in comparison to the control group (p<0.05). Meanwhile, treated HCC group had lower expression levels of Adar1 in comparison to untreated HCC rats. Conclusions pterostilbene had a beneficial effect on HCC and it may alleviate the aberrant expression of Adar1 in HCC rats. Key words HCC, ADARs, pterostilbene, RNA editing enzymes. Acknowledgments: No finical support was present Conflict of interest: the authors declared that no conflicts of interest concerning the article. Authors’ contributions: The authors contributed to the design and implementation of the research, to the analysis of the results and to the writing of the manuscript

scholarly journals Missense Mutation in the Transcription Factor NKX2–5: A Novel Molecular Event in the Pathogenesis of Thyroid Dysgenesis

2006 ◽  
Vol 91 (4) ◽  
pp. 1428-1433 ◽  
Author(s):  
Monica Dentice ◽  
Viviana Cordeddu ◽  
Annamaria Rosica ◽  
Alfonso Massimiliano Ferrara ◽  
Libero Santarpia ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Transcription Factor ◽  
Heart Disease ◽  
Heart Development ◽  
Congenital Heart ◽  
Functional Characterization ◽  
Dominant Negative Effect ◽  
Thyroid Dysgenesis ◽  
Thyroid Development

Context: Congenital hypothyroidism (CH) is a common endocrine disorder with an incidence of 1:3000–4000 at birth. In 80–85% of cases, CH is caused by defects in thyroid organogenesis, resulting in absent, ectopically located, and/or severely reduced gland [thyroid dysgenesis (TD)]. Mutations in genes controlling thyroid development have demonstrated that in a few cases, TD is a Mendelian trait. However, accumulating evidence supports the view that the genetics of TD are complex, possibly with a polygenic/multifactorial basis. A higher prevalence of congenital heart disease has been documented in children with CH than in the general population. Such an association suggests a possible pathogenic role of genes involved in both heart and thyroid development. NKX2–5 encodes a homeodomain-containing transcription factor with a major role in heart development, and mutations affecting this gene have been reported in individuals with congenital heart disease. Objective: In the present work we investigated the possible involvement of NKX2–5 mutations in TD. Results: Our results indicate that Nkx2–5−/− embryos exhibit thyroid bud hypoplasia, providing evidence that NKX2–5 plays a role in thyroid organogenesis and that NKX2–5 mutations contribute to TD. NKX2–5 mutational screening in 241 patients with TD allowed the identification of three heterozygous missense changes (R25C, A119S, and R161P) in four patients with TD. Functional characterization of the three mutations demonstrated reduced DNA binding and/or transactivation properties, with a dominant-negative effect on wild-type NKX2–5. Conclusion: Our results suggest a previously unknown role of NKX2–5 in the pathogenesis of TD.

scholarly journals KCNQ1OT1: An Oncogenic Long Noncoding RNA

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1602
Author(s):  
Patrice Cagle ◽  
Qi Qi ◽  
Suryakant Niture ◽  
Deepak Kumar
Keyword(s):  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Vital Role ◽  
Migration And Invasion ◽  
Biological Functions ◽  
Aberrant Expression ◽  
Human Cancers ◽  
Oral Melanoma ◽  
Opposite Strand

Long noncoding RNAs (lncRNAs) are transcripts greater than 200 nucleotides that do not code for proteins but regulate gene expression. Recent studies indicate that lncRNAs are involved in the modulation of biological functions in human disease. KCNQ1 Opposite Strand/Antisense Transcript 1 (KCNQ1OT1) encodes a lncRNA from the opposite strand of KCNQ1 in the CDKN1C/KCNQ1OT1 cluster that is reported to play a vital role in the development and progression of cancer. KCNQ1OT1 regulates cancer cell proliferation, cell cycle, migration and invasion, metastasis, glucose metabolism, and immune evasion. The aberrant expression of KCNQ1OT1 in cancer patients is associated with poor prognosis and decreased survival. This review summarizes recent literature related to the biological functions and molecular mechanisms of KCNQ1OT1 in various human cancers, including colorectal, bladder, breast, oral, melanoma, osteosarcoma, lung, glioma, ovarian, liver, acute myeloid leukemia, prostate, and gastric. We also discuss the role of KCNQ1OT1 as a promising diagnostic biomarker and a novel therapeutic target in human cancers.

scholarly journals N6-Methyladenosine Landscape of Glioma Stem-Like Cells: METTL3 Is Essential for the Expression of Actively Transcribed Genes and Sustenance of the Oncogenic Signaling

Genes ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 141 ◽  
Author(s):  
Abhirami Visvanathan ◽  
Vikas Patil ◽  
Shibla Abdulla ◽  
Jörg Hoheisel ◽  
Kumaravel Somasundaram
Keyword(s):  
Rna Editing ◽  
Rna Processing ◽  
Vital Role ◽  
Integrated Analysis ◽  
Oncogenic Signaling ◽  
Protein Coding ◽  
Oncogenic Pathways ◽  
Successful Execution ◽  
Rna Immunoprecipitation ◽  
Rna Stabilization

Despite recent advances in N6-methyladenosine (m6A) biology, the regulation of crucial RNA processing steps by the RNA methyltransferase-like 3 (METTL3) in glioma stem-like cells (GSCs) remains obscure. An integrated analysis of m6A-RIP (RNA immunoprecipitation) and total RNA-Seq of METTL3-silenced GSCs identified that m6A modification in GSCs is principally carried out by METTL3. The m6A-modified transcripts showed higher abundance compared to non-modified transcripts. Further, we showed that the METTL3 is essential for the expression of GSC-specific actively transcribed genes. Silencing METTL3 resulted in the elevation of several aberrant alternative splicing events. We also found that putative m6A reader proteins play a key role in the RNA stabilization function of METTL3. METTL3 altered A-to-I and C-to-U RNA editing events by differentially regulating RNA editing enzymes ADAR and APOBEC3A. Similar to protein-coding genes, lincRNAs (long intergenic non-coding RNAs) with m6A marks showed METTL3-dependent high expression. m6A modification of 3′UTRs appeared to result in a conformation-dependent hindrance to miRNA binding to their targets. The integrated analysis of the m6A regulome in METTL3-silenced GSCs showed global disruption in tumorigenic pathways that are indispensable for GSC maintenance and glioma progression. We conclude that METTL3 plays a vital role in many steps of RNA processing and orchestrates successful execution of oncogenic pathways in GSCs.

scholarly journals Epicardial TGFβ and BMP Signaling in Cardiac Regeneration: What Lesson Can We Learn from the Developing Heart?

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 404
Author(s):  
Esther Dronkers ◽  
Manon M. M. Wauters ◽  
Marie José Goumans ◽  
Anke M. Smits
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Transforming Growth Factor ◽  
Current Knowledge ◽  
Transforming Growth Factor Β ◽  
Heart Tissue ◽  
Vital Role ◽  
Bmp Signaling ◽  
Mesenchymal Transition ◽  
Starting Point

The epicardium, the outer layer of the heart, has been of interest in cardiac research due to its vital role in the developing and diseased heart. During development, epicardial cells are active and supply cells and paracrine cues to the myocardium. In the injured adult heart, the epicardium is re-activated and recapitulates embryonic behavior that is essential for a proper repair response. Two indispensable processes for epicardial contribution to heart tissue formation are epithelial to mesenchymal transition (EMT), and tissue invasion. One of the key groups of cytokines regulating both EMT and invasion is the transforming growth factor β (TGFβ) family, including TGFβ and Bone Morphogenetic Protein (BMP). Abundant research has been performed to understand the role of TGFβ family signaling in the developing epicardium. However, less is known about signaling in the adult epicardium. This review provides an overview of the current knowledge on the role of TGFβ in epicardial behavior both in the development and in the repair of the heart. We aim to describe the presence of involved ligands and receptors to establish if and when signaling can occur. Finally, we discuss potential targets to improve the epicardial contribution to cardiac repair as a starting point for future investigation.

scholarly journals Deregulated Cardiac Specific MicroRNAs in Postnatal Heart Growth

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Pujiao Yu ◽  
Hongbao Wang ◽  
Yuan Xie ◽  
Jinzhe Zhou ◽  
Jianhua Yao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Development ◽  
Growth Period ◽  
Heart Tissue ◽  
Postnatal Period ◽  
Multiple Systems ◽  
Functional Annotations ◽  
Qrt Pcr ◽  
Kegg Analysis

The heart is recognized as an organ that is terminally differentiated by adulthood. However, during the process of human development, the heart is the first organ with function in the embryo and grows rapidly during the postnatal period. MicroRNAs (miRNAs, miRs), as regulators of gene expression, play important roles during the development of multiple systems. However, the role of miRNAs in postnatal heart growth is still unclear. In this study, by using qRT-PCR, we compared the expression of seven cardiac- or muscle-specific miRNAs that may be related to heart development in heart tissue from mice at postnatal days 0, 3, 8, and 14. Four miRNAs—miR-1a-3p, miR-133b-3p, miR-208b-3p, and miR-206-3p—were significantly decreased while miR-208a-3p was upregulated during the postnatal heart growth period. Based on these results, GeneSpring GX was used to predict potential downstream targets by performing a 3-way comparison of predictions from the miRWalk, PITA, and microRNAorg databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to identify potential functional annotations and signaling pathways related to postnatal heart growth. This study describes expression changes of cardiac- and muscle-specific miRNAs during postnatal heart growth and may provide new therapeutic targets for cardiovascular diseases.

scholarly journals Bioinformatics Analysis and Identification of the Expression and Mechanism of Immune-related Gene MAPT in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Yan Jiang ◽  
Duan-kai Chen ◽  
Fa-hui Liu ◽  
Qi-ming Gong ◽  
Chen-yi Zhuo ◽  
...  
Keyword(s):  
Bioinformatics Analysis ◽  
Survival Curve ◽  
Enrichment Analysis ◽  
R Package ◽  
Gene Set Enrichment Analysis ◽  
Aberrant Expression ◽  
Protein Coding ◽  
Related Data ◽  
Kaplan Meier

Abstract MAPT (Microtubule Associated Protein Tau) is a Protein Coding gene. Aberrant expression of MAPT has been reported to be associated with several types of tumors, such as gastric, breast, and colorectal cancer, and so on. However, the role of MAPT in HCC (Hepatic carcinoma) is still poorly understood. In our research, MAPT-related data mining and analyzing were used publicly-available data from TCGA, GEO, Oncomine, and HPA databases. The survival curve was shown and analyzed by using Kaplan Meier Plotter. Gene Set Enrichment Analysis (GSEA), TIMER, STRING, and R package were used to explore the function and potential mechanism of MAPT in HCC. The results show that MAPT is overexpressed in HCC samples and is correlated with worse prognosis of patients with HCC. Bioinformatics analysis showed that MAPT contributed to the development of tumors through a variety of mechanisms. In conclusion, the Up-regulation of MAPT was significantly linked to poor prognosis in HCC patients, and it could be a new therapeutic target for HCC therapy.

scholarly journals Essential Role of Endothelial Smad4 in Vascular Remodeling and Integrity

2007 ◽  
Vol 27 (21) ◽  
pp. 7683-7692 ◽  
Author(s):  
Yu Lan ◽  
Bing Liu ◽  
Huiyu Yao ◽  
Fangfei Li ◽  
Tujun Weng ◽  
...  
Keyword(s):  
Tube Formation ◽  
Intrinsic Defect ◽  
P System ◽  
Aberrant Expression ◽  
Vascular Integrity ◽  
Mural Cells ◽  
Vessel Remodeling ◽  
Cardiovascular Defects

ABSTRACT New blood vessels are formed through the assembly or sprouting of endothelial cells (ECs) and become stabilized by the formation of perivascular matrix and the association with supporting mural cells. To investigate the role of endothelial Smad4 in vascular development, we deleted the Smad4 gene specifically in ECs using the Cre-LoxP system. EC-specific Smad4 mutant mice died at embryonic day 10.5 due to cardiovascular defects, including attenuated vessels sprouting and remodeling, collapsed dorsal aortas, enlarged hearts with reduced trabeculae, and failed endocardial cushion formation. Noticeably, Smad4-deficient ECs demonstrated an intrinsic defect in tube formation in vitro. Furthermore, the mutant vascular ECs dissociated away from the surrounding cells and suffered from impaired development of vascular smooth muscle cells. The disturbed vascular integrity and maturation was associated with aberrant expression of angiopoietins and a gap junction component, connexin43. Collectively, we have provided direct functional evidence that Smad4 activity in the developing ECs is essential for blood vessel remodeling, maturation, and integrity.

Asiana Airlines Flight 214

2014 ◽  
Vol 4 (2) ◽  
pp. 113-121 ◽  
Author(s):  
Stephanie Chow ◽  
Stephen Yortsos ◽  
Najmedin Meshkati
Keyword(s):  
Human Factors ◽  
Aviation Safety ◽  
Cultural Factors ◽  
Vital Role ◽  
Cultural Issues ◽  
Flight Crew ◽  
Pilot Performance ◽  
Engineering Designs ◽  
Flight Deck

This article focuses on a major human factors–related issue that includes the undeniable role of cultural factors and cockpit automation and their serious impact on flight crew performance, communication, and aviation safety. The report concentrates on the flight crew performance of the Boeing 777–Asiana Airlines Flight 214 accident, by exploring issues concerning mode confusion and autothrottle systems. It also further reviews the vital role of cultural factors in aviation safety and provides a brief overview of past, related accidents. Automation progressions have been created in an attempt to design an error-free flight deck. However, to do that, the pilot must still thoroughly understand every component of the flight deck – most importantly, the automation. Otherwise, if pilots are not completely competent in terms of their automation, the slightest errors can lead to fatal accidents. As seen in the case of Asiana Flight 214, even though engineering designs and pilot training have greatly evolved over the years, there are many cultural, design, and communication factors that affect pilot performance. It is concluded that aviation systems designers, in cooperation with pilots and regulatory bodies, should lead the strategic effort of systematically addressing the serious issues of cockpit automation, human factors, and cultural issues, including their interactions, which will certainly lead to better solutions for safer flights.

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