scholarly journals MicroRNAs as Potential Biomarkers in Atherosclerosis

2019 ◽  
Vol 20 (22) ◽  
pp. 5547 ◽  
Author(s):  
Alexey Churov ◽  
Volha Summerhill ◽  
Andrey Grechko ◽  
Varvara Orekhova ◽  
Alexander Orekhov
Keyword(s):  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Inflammatory Cells ◽  
Cellular Protein ◽  
Cholesterol Homeostasis ◽  
Transcriptional Level ◽  
High Morbidity ◽  
Industrialized Countries ◽  
Rna Molecules ◽  
Expression Of Genes

Atherosclerosis is a complex multifactorial disease that, despite advances in lifestyle management and drug therapy, remains to be the major cause of high morbidity and mortality rates from cardiovascular diseases (CVDs) in industrialized countries. Therefore, there is a great need in reliable diagnostic/prognostic biomarkers and effective treatment alternatives to reduce its burden. It was established that microRNAs (miRNAs/miRs), a class of non-coding single-stranded RNA molecules, can regulate the expression of genes at the post-transcriptional level and, accordingly, coordinate the cellular protein expression. Thus, they are involved not only in cell-specific physiological functions but also in the cellular and molecular mechanisms of human pathologies, including atherosclerosis. MiRNAs may be significant in the dysregulation that affects endothelial integrity, the function of vascular smooth muscle and inflammatory cells, and cellular cholesterol homeostasis that drives the initiation and growth of an atherosclerotic plaque. Besides, distinct expression patterns of several miRNAs are attributed to atherosclerotic and cardiovascular patients. In this article, the evidence indicating the multiple critical roles of miRNAs and their relevant molecular mechanisms related to atherosclerosis development and progression was reviewed. Moreover, the effects of miRNAs on atherosclerosis enabled to exploit them as novel diagnostic biomarkers and therapeutic targets that may lead to better management of atherosclerosis and CVDs.

scholarly journals Poplar protease inhibitor expression differs in an herbivore specific manner

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Franziska Eberl ◽  
Thomas Fabisch ◽  
Katrin Luck ◽  
Tobias G. Köllner ◽  
Heiko Vogel ◽  
...  
Keyword(s):  
Protease Inhibitors ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Transcriptional Level ◽  
Species Identity ◽  
Defense Proteins ◽  
Woody Perennials ◽  
Cdna Sequences ◽  
Black Poplar ◽  
Leaf Area Loss

Abstract Background Protease inhibitors are defense proteins widely distributed in the plant kingdom. By reducing the activity of digestive enzymes in insect guts, they reduce the availability of nutrients and thus impair the growth and development of the attacking herbivore. One well-characterized class of protease inhibitors are Kunitz-type trypsin inhibitors (KTIs), which have been described in various plant species, including Populus spp. Long-lived woody perennials like poplar trees encounter a huge diversity of herbivores, but the specificity of tree defenses towards different herbivore species is hardly studied. We therefore aimed to investigate the induction of KTIs in black poplar (P. nigra) leaves upon herbivory by three different chewing herbivores, Lymantria dispar and Amata mogadorensis caterpillars, and Phratora vulgatissima beetles. Results We identified and generated full-length cDNA sequences of 17 KTIs that are upregulated upon herbivory in black poplar leaves, and analyzed the expression patterns of the eight most up-regulated KTIs via qRT-PCR. We found that beetles elicited higher transcriptional induction of KTIs than caterpillars, and that both caterpillar species induced similar KTI expression levels. Furthermore, KTI expression strongly correlated with the trypsin-inhibiting activity in the herbivore-damaged leaves, but was not dependent on damage severity, i.e. leaf area loss, for most of the genes. Conclusions We conclude that the induction of KTIs in black poplar is controlled at the transcriptional level in a threshold-based manner and is strongly influenced by the species identity of the herbivore. However, the underlying molecular mechanisms and ecological consequences of these patterns remain to be investigated.

Drugs used to treat bipolar disorder act via microRNAs to regulate expression of genes involved in neurite outgrowth

2020 ◽  
Vol 34 (3) ◽  
pp. 370-379 ◽  
Author(s):  
Srisaiyini Kidnapillai ◽  
Ben Wade ◽  
Chiara C Bortolasci ◽  
Bruna Panizzutti ◽  
Briana Spolding ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Neurite Outgrowth ◽  
Neural Plasticity ◽  
Drug Combination ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Drug Effects ◽  
Differentially Expressed ◽  
Transcriptional Level ◽  
Expression Of Genes

Background: The drugs commonly used to treat bipolar disorder have limited efficacy and drug discovery is hampered by the paucity of knowledge of the pathophysiology of this disease. This study aims to explore the role of microRNAs in bipolar disorder and understand the molecular mechanisms of action of commonly used bipolar disorder drugs. Methods: The transcriptional effects of bipolar disorder drug combination (lithium, valproate, lamotrigine and quetiapine) in cultured human neuronal cells were studied using next generation sequencing. Differential expression of genes ( n=20) and microRNAs ( n=6) was assessed and the differentially expressed microRNAs were confirmed with TaqMan MicroRNA Assays. The expression of the differentially expressed microRNAs were inhibited to determine bipolar disorder drug effects on their target genes ( n=8). Independent samples t-test was used for normally distributed data and Kruskal-Wallis/Mann-Whitney U test was used for data not distributed normally. Significance levels were set at p<0.05. Results: We found that bipolar disorder drugs tended to increase the expression of miR-128 and miR-378 ( p<0.05). Putative target genes of these microRNAs targeted pathways including those identified as “neuron projection development” and “axonogenesis”. Many of the target genes are inhibitors of neurite outgrowth and neurogenesis and were downregulated following bipolar disorder drug combination treatment (all p<0.05). The bipolar disorder drug combination tended to decrease the expression of the target genes ( NOVA1, GRIN3A, and VIM), however this effect could be reversed by the application of microRNA inhibitors. Conclusions: We conclude that at a transcriptional level, bipolar disorder drugs affect several genes in concert that would increase neurite outgrowth and neurogenesis and hence neural plasticity, and that this effect is mediated (at least in part) by modulation of the expression of these two key microRNAs.

scholarly journals Novel Insights into the Protective Properties of ACTH(4-7)PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia–Reperfusion in Rats

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 681 ◽  
Author(s):  
Ivan B. Filippenkov ◽  
Vasily V. Stavchansky ◽  
Alina E. Denisova ◽  
Vadim V. Yuzhakov ◽  
Larisa E. Sevan’kaeva ◽  
...  
Keyword(s):  
Cerebral Ischaemia ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Artery Occlusion ◽  
Biologically Active ◽  
Protective Properties ◽  
Ischaemia Reperfusion ◽  
Expression Of Genes ◽  
The Brain ◽  
Transcriptome Level

Cerebral ischaemia is the most common cause of impaired brain function. Biologically active peptides represent potential drugs for reducing the damage that occurs after ischaemia. The synthetic melanocortin derivative, ACTH(4-7)PGP (Semax), has been used successfully in the treatment of patients with severe impairment of cerebral blood circulation. However, its molecular mechanisms of action within the brain are not yet fully understood. Previously, we used the transient middle cerebral artery occlusion (tMCAO) model to study the damaging effects of ischaemia–reperfusion on the brain transcriptome in rats. Here, using RNA-Seq analysis, we investigated the protective properties of the Semax peptide at the transcriptome level under tMCAO conditions. We have identified 394 differentially expressed genes (DEGs) (>1.5-fold change) in the brains of rats at 24 h after tMCAO treated with Semax relative to saline. Following tMCAO, we found that Semax suppressed the expression of genes related to inflammatory processes and activated the expression of genes related to neurotransmission. In contrast, ischaemia–reperfusion alone activated the expression of inflammation-related genes and suppressed the expression of neurotransmission-related genes. Therefore, the neuroprotective action of Semax may be associated with a compensation of mRNA expression patterns that are disrupted during ischaemia–reperfusion conditions.

scholarly journals MicroRNAs in Uteroplacental Vascular Dysfunction

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1344 ◽  
Author(s):  
Hu ◽  
Zhang
Keyword(s):  
Intrauterine Growth Restriction ◽  
Target Genes ◽  
Vascular Dysfunction ◽  
Neonatal Morbidity ◽  
Trophoblast Invasion ◽  
Transcriptional Level ◽  
Regulate Gene Expression ◽  
Rna Molecules ◽  
Expression Of Genes ◽  
Differentially Expressed Mirnas

Pregnancy complications of preeclampsia and intrauterine growth restriction (IUGR) are major causes of maternal and perinatal/neonatal morbidity and mortality. Although their etiologies remain elusive, it is generally accepted that they are secondary to placental insufficiency conferred by both failure in spiral artery remodeling and uteroplacental vascular malfunction. MicroRNAs (miRNAs) are small no-coding RNA molecules that regulate gene expression at the post-transcriptional level. Increasing evidence suggests that miRNAs participate in virtually all biological processes and are involved in numerous human diseases. Differentially expressed miRNAs in the placenta are typical features of both preeclampsia and IUGR. Dysregulated miRNAs target genes of various signaling pathways in uteroplacental tissues, contributing to the development of both complications. In this review, we provide an overview of how aberrant miRNA expression in preeclampsia and IUGR impacts the expression of genes involved in trophoblast invasion and uteroplacental vascular adaptation.

scholarly journals Genomic analyses of early responses to radiation in glioblastoma reveal new alterations at transcription, splicing, and translation levels

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Saket Choudhary ◽  
Suzanne C. Burns ◽  
Hoda Mirsafian ◽  
Wenzheng Li ◽  
Dat T. Vo ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Early Response ◽  
Radiation Sensitivity ◽  
Integrated Analysis ◽  
High Dose ◽  
Transcriptional Level ◽  
Altered Expression ◽  
Expression Of Genes ◽  
Post Radiation ◽  
Main Component

Abstract High-dose radiation is the main component of glioblastoma therapy. Unfortunately, radio-resistance is a common problem and a major contributor to tumor relapse. Understanding the molecular mechanisms driving response to radiation is critical for identifying regulatory routes that could be targeted to improve treatment response. We conducted an integrated analysis in the U251 and U343 glioblastoma cell lines to map early alterations in the expression of genes at three levels: transcription, splicing, and translation in response to ionizing radiation. Changes at the transcriptional level were the most prevalent response. Downregulated genes are strongly associated with cell cycle and DNA replication and linked to a coordinated module of expression. Alterations in this group are likely driven by decreased expression of the transcription factor FOXM1 and members of the E2F family. Genes involved in RNA regulatory mechanisms were affected at the mRNA, splicing, and translation levels, highlighting their importance in radiation-response. We identified a number of oncogenic factors, with an increased expression upon radiation exposure, including BCL6, RRM2B, IDO1, FTH1, APIP, and LRIG2 and lncRNAs NEAT1 and FTX. Several of these targets have been previously implicated in radio-resistance. Therefore, antagonizing their effects post-radiation could increase therapeutic efficacy. Our integrated analysis provides a comprehensive view of early response to radiation in glioblastoma. We identify new biological processes involved in altered expression of various oncogenic factors and suggest new target options to increase radiation sensitivity and prevent relapse.

scholarly journals MicroRNAs in Obesity and Related Metabolic Disorders

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 859 ◽  
Author(s):  
Jean-François Landrier ◽  
Adel Derghal ◽  
Lourdes Mounien
Keyword(s):  
Metabolic Disease ◽  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Untranslated Regions ◽  
Rna Molecules ◽  
Expression Of Genes ◽  
Non Coding Rna ◽  
Micro Rnas

Metabolic disorders are characterized by the inability to properly use and/or store energy. The burdens of metabolic disease, such as obesity or diabetes, are believed to arise through a complex interplay between genetics and epigenetics predisposition, environment and nutrition. Therefore, understanding the molecular mechanisms for the onset of metabolic disease will provide new insights for prevention and treatment. There is growing concern about the dysregulation of micro-RNAs (miRNAs) in metabolic diseases. MiRNAs are short non-coding RNA molecules that post-transcriptionally repress the expression of genes by binding to untranslated regions and coding sequences of the target mRNAs. This review aims to provide recent data about the potential involvement of miRNAs in metabolic diseases, particularly obesity and type 2 diabetes.

scholarly journals Regulatory roles and mechanisms of alternative RNA splicing in adipogenesis and human metabolic health

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yunqi Chao ◽  
Yonghui Jiang ◽  
Mianling Zhong ◽  
Kaiyan Wei ◽  
Chenxi Hu ◽  
...  
Keyword(s):  
Rna Splicing ◽  
Expression Patterns ◽  
Treatment Strategies ◽  
Cellular Protein ◽  
Transcriptional Level ◽  
Altered Expression ◽  
Splicing Regulators ◽  
Diet Induced Obesity ◽  
Metabolic Dysregulation ◽  
Beige Adipocytes

AbstractAlternative splicing (AS) regulates gene expression patterns at the post-transcriptional level and generates a striking expansion of coding capacities of genomes and cellular protein diversity. RNA splicing could undergo modulation and close interaction with genetic and epigenetic machinery. Notably, during the adipogenesis processes of white, brown and beige adipocytes, AS tightly interplays with the differentiation gene program networks. Here, we integrate the available findings on specific splicing events and distinct functions of different splicing regulators as examples to highlight the directive biological contribution of AS mechanism in adipogenesis and adipocyte biology. Furthermore, accumulating evidence has suggested that mutations and/or altered expression in splicing regulators and aberrant splicing alterations in the obesity-associated genes are often linked to humans’ diet-induced obesity and metabolic dysregulation phenotypes. Therefore, significant attempts have been finally made to overview novel detailed discussion on the prospects of splicing machinery with obesity and metabolic disorders to supply featured potential management mechanisms in clinical applicability for obesity treatment strategies.

scholarly journals Integrated analyses of early responses to radiation in glioblastoma identify new alterations in RNA processing and candidate targets to improve treatment outcomes

2020 ◽  
Author(s):  
Saket Choudhary ◽  
Suzanne Burns ◽  
Hoda Mirsafian ◽  
Whenzheng LI ◽  
Dat Vo ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Early Response ◽  
Radiation Sensitivity ◽  
Integrated Analysis ◽  
High Dose ◽  
Transcriptional Level ◽  
Altered Expression ◽  
Improve Treatment ◽  
Expression Of Genes ◽  
Main Component

Abstract BackgroundHigh-dose radiation is the main component of glioblastoma therapy. Unfortunately, radio-resistance is a common problem and a major contributor to tumor relapse. Understanding the molecular mechanisms driving response to radiation is critical for identifying regulatory routes that could be targeted to improve treatment response. Methods: We conducted an integrated analysis in the U251 and U343 glioblastoma cell lines to map early alterations in the expression of genes at three levels: transcription, splicing, and translation in response to ionizing radiation. ResultsChanges at the transcriptional level were the most prevalent response. Downregulated genes are strongly associated with cell cycle and DNA replication and linked to a coordinated module of expression. Alterations in this group are likely driven by decreased expression of the transcription factor FOXM1 and members of the E2F family. Genes involved in RNA regulatory mechanisms were affected at the mRNA, splicing, and translation levels, highlighting their importance in radiation-response. We identified a number of oncogenic factors, with an increased expression upon radiation exposure, including BCL6, RRM2B, IDO1, FTH1, APIP, and LRIG2 and lncRNAs NEAT1 and FTX. Several of these targets have been previously implicated in radio- resistance. Therefore, antagonizing their effects post-radiation could increase therapeutic efficacy. ConclusionsOur integrated analysis provides a comprehensive view of early response to radiation in glioblastoma. We identify new biological processes involved in altered expression of various oncogenic factors and suggest new target options to increase radiation sensitivity and prevent relapse.

scholarly journals The landscape of transcriptional and translational changes over 22 years of bacterial adaptation

2021 ◽  
Author(s):  
John S. Favate ◽  
Shun Liang ◽  
Srujana S. Yadavalli ◽  
Premal Shah
Keyword(s):  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Transcriptional Level ◽  
Genomic Changes ◽  
E Coli ◽  
Fitness Effects ◽  
Term Evolution ◽  
Evolution Experiment ◽  
Genetic Level

AbstractOrganisms can adapt to an environment by taking multiple mutational paths. This redundancy at the genetic level, where many mutations have similar phenotypic and fitness effects, can make untangling the molecular mechanisms of complex adaptations difficult. Here we use the E. coli long-term evolution experiment (LTEE) as a model to address this challenge. To bridge the gap between disparate genomic changes and parallel fitness gains, we characterize the landscape of transcriptional and translational changes across 11 replicate populations evolving in parallel for 50,000 generations. By quantifying absolute changes in mRNA abundances, we show that not only do all evolved lines have more mRNAs but that this increase in mRNA abundance scales with cell size. We also find that despite few shared mutations at the genetic level, clones from replicate populations in the LTEE are remarkably similar to each other in their gene expression patterns at both the transcriptional and translational levels. Furthermore, we show that the bulk of the expression changes are due to changes at the transcriptional level with very few translational changes. Finally, we show how mutations in transcriptional regulators lead to consistent and parallel changes in the expression levels of downstream genes, thereby linking genomic changes to parallel fitness gains in the LTEE. These results deepen our understanding of the molecular mechanisms underlying complex adaptations and provide insights into the repeatability of evolution.

scholarly journals The transcriptional events and their relationship to physiological changes during poplar seed germination and post-germination

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Chunpu Qu ◽  
Hancheng Zhao ◽  
Jinyuan Chen ◽  
Zhuang Zuo ◽  
Xue Sun ◽  
...  
Keyword(s):  
Seed Germination ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Atp Synthesis ◽  
Enrichment Analysis ◽  
Transcriptional Level ◽  
Primary Metabolism ◽  
Expression Of Genes ◽  
Molecular Events ◽  
Acid Protein

Abstract Background Seed germination, the foundation of plant propagation, involves a series of changes at the molecular level. Poplar is a model woody plant, but the molecular events occurring during seed germination in this species are unclear. Results In this study, we investigated changes in gene transcriptional levels during different germination periods in poplar by high-throughput sequencing technology. Analysis of genes expressed at specific germination stages indicated that these genes are distributed in many metabolic pathways. Enrichment analysis of significantly differentially expressed genes based on hypergeometric testing revealed that multiple pathways, such as pathways related to glycolysis, lipid, amino acid, protein and ATP synthesis metabolism, changed significantly at the transcriptional level during seed germination. A comparison of ΣZ values uncovered a series of transcriptional changes in biological processes related to primary metabolism during poplar seed germination. Among these changes, genes related to CHO metabolism were the first to be activated, with subsequent expression of genes involved in lipid metabolism and then those associated with protein metabolism. The pattern of metabolomic and physiological index changes further verified the sequence of some biological events. Conclusions Our study revealed molecular events occurring at the transcriptional level during seed germination and determined their order. These events were further verified by patterns of changes of metabolites and physiological indexes. Our findings lay a foundation for the elucidation of the molecular mechanisms responsible for poplar seed germination.

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