Decoding resistant hypertension signalling pathways

2017 ◽  
Vol 131 (23) ◽  
pp. 2813-2834 ◽  
Author(s):  
Ricardo Cambraia Parreira ◽  
Leandro Heleno Guimarães Lacerda ◽  
Rebecca Vasconcellos ◽  
Swiany Silveira Lima ◽  
Anderson Kenedy Santos ◽  
...  
Keyword(s):  
Resistant Hypertension ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Signalling Pathways ◽  
Transcriptional Level ◽  
Cardiovascular Damage ◽  
Current State ◽  
Cardiovascular Morbidity And Mortality ◽  
Non Coding Rnas ◽  
Therapeutic Tools

Resistant hypertension (RH) is a clinical condition in which the hypertensive patient has become resistant to drug therapy and is often associated with increased cardiovascular morbidity and mortality. Several signalling pathways have been studied and related to the development and progression of RH: modulation of sympathetic activity by leptin and aldosterone, primary aldosteronism, arterial stiffness, endothelial dysfunction and variations in the renin–angiotensin–aldosterone system (RAAS). miRNAs comprise a family of small non-coding RNAs that participate in the regulation of gene expression at post-transcriptional level. miRNAs are involved in the development of both cardiovascular damage and hypertension. Little is known of the molecular mechanisms that lead to development and progression of this condition. This review aims to cover the potential roles of miRNAs in the mechanisms associated with the development and consequences of RH, and explore the current state of the art of diagnostic and therapeutic tools based on miRNA approaches.

scholarly journals The miR-302/367 cluster: a comprehensive update on its evolution and functions

Open Biology ◽  
2015 ◽  
Vol 5 (12) ◽  
pp. 150138 ◽  
Author(s):  
Zeqian Gao ◽  
Xueliang Zhu ◽  
Yongxi Dou
Keyword(s):  
Evolutionary History ◽  
Regulation Of Gene Expression ◽  
Embryonic Stem ◽  
Signalling Pathways ◽  
Transcriptional Level ◽  
Biological Processes ◽  
Related Protein ◽  
Non Coding Rnas ◽  
Cycle Regulation ◽  
Fine Tune

microRNAs are a subclass of small non-coding RNAs that fine-tune the regulation of gene expression at the post-transcriptional level. The miR-302/367 cluster, generally consisting of five members, miR-367, miR-302d, miR-302a, miR-302c and miR-302b, is ubiquitously distributed in vertebrates and occupies an intragenic cluster located in the gene La-related protein 7 ( LARP7 ). The cluster was demonstrated to play an important role in diverse biological processes, such as the pluripotency of human embryonic stem cells (hESCs), self-renewal and reprogramming. This paper provides an overview of the mir-302/367 cluster, discusses our current understanding of the cluster's evolutionary history and transcriptional regulation and reviews the literature surrounding the cluster's roles in cell cycle regulation, epigenetic regulation and different cellular signalling pathways.

scholarly journals Deciphering the Role of MicroRNAs in Neuroblastoma

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 99
Author(s):  
Vishnu Priya Veeraraghavan ◽  
Selvaraj Jayaraman ◽  
Gayathri Rengasamy ◽  
Ullas Mony ◽  
Dhanraj M Ganapathy ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Considerable Increase ◽  
Treatment Strategies ◽  
Signalling Pathways ◽  
Current State ◽  
Advanced Stages ◽  
Non Coding Rnas ◽  
New Treatment ◽  
Peripheral Sympathetic Nervous System

Neuroblastoma (NB) is a type of peripheral sympathetic nervous system cancer that most commonly affects children. It is caused by the improper differentiation of primitive neural crest cells during embryonic development. Although NB occurs for 8% of paediatric cancers, it accounts for 15% of cancer-related deaths. Despite a considerable increase in cytotoxic chemo- and radiotherapy, patients in advanced stages remain virtually incurable. Therefore, there is a desperate necessity for new treatment strategies to be investigated. Accumulating evidence suggested that microRNAs (miRNAs) are a class of non-coding RNAs with 19–25 nucleotides lengths and play a central role in the development of NB carcinogenesis. Fascinatingly, miRNA inhibitors have an antisense property that can inhibit miRNA function and suppress the activity of mature miRNA. However, many studies have addressed miRNA inhibition in the treatment of NB, but their molecular mechanisms and signalling pathways are yet to be analysed. In this study, we impart the current state of knowledge about the role of miRNA inhibition in the aetiology of NB.

scholarly journals Long non-coding RNAs in brain tumors

NAR Cancer ◽  
2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Keisuke Katsushima ◽  
George Jallo ◽  
Charles G Eberhart ◽  
Ranjan J Perera
Keyword(s):  
Gene Expression ◽  
Brain Tumors ◽  
Brain Cancer ◽  
Regulation Of Gene Expression ◽  
Therapeutic Targets ◽  
Diagnostic Biomarkers ◽  
Cancer Pathogenesis ◽  
Current State ◽  
Non Coding Rnas ◽  
Post Transcriptional Regulation

Abstract Long non-coding RNAs (lncRNAs) have been found to be central players in the epigenetic, transcriptional and post-transcriptional regulation of gene expression. There is an accumulation of evidence on newly discovered lncRNAs, their molecular interactions and their roles in the development and progression of human brain tumors. LncRNAs can have either tumor suppressive or oncogenic functions in different brain cancers, making them attractive therapeutic targets and biomarkers for personalized therapy and precision diagnostics. Here, we summarize the current state of knowledge of the lncRNAs that have been implicated in brain cancer pathogenesis, particularly in gliomas and medulloblastomas. We discuss their epigenetic regulation as well as the prospects of using lncRNAs as diagnostic biomarkers and therapeutic targets in patients with brain tumors.

DLX6-AS1: a putative lncRNA candidate in multiple human cancers

2021 ◽  
Vol 23 ◽  
Author(s):  
Mohsen Sheykhhasan ◽  
Yaghoub Ahmadyousefi ◽  
Reihaneh Seyedebrahimi ◽  
Hamid Tanzadehpanah ◽  
Hamed Manoochehri ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Critical Analysis ◽  
Molecular Mechanisms ◽  
Signalling Pathways ◽  
Biological Functions ◽  
Initial Development ◽  
Human Cancers ◽  
Expression Of Genes ◽  
Non Coding Rnas ◽  
Research Studies

Abstract Long non-coding RNAs (lncRNAs) have important roles in regulating the expression of genes and act as biomarkers in the initial development of different cancers. Increasing research studies have verified that dysregulation of lncRNAs occurs in various pathological processes including tumorigenesis and cancer progression. Among the different lncRNAs, DLX6-AS1 has been reported to act as an oncogene in the development and prognoses of different cancers, by affecting many different signalling pathways. This review summarises and analyses the recent research studies describing the biological functions of DLX6-AS1, its overall effect on signalling pathways and the molecular mechanisms underlying its action on the expression of genes in multiple human cancers. Our critical analysis suggests that different signalling pathways associated to this lncRNA may be used as a biomarker for diagnosis, or targets of treatment in cancers.

scholarly journals Sex-Specific MicroRNAs in Neurovascular Units in Ischemic Stroke

2021 ◽  
Vol 22 (21) ◽  
pp. 11888
Author(s):  
Barend W. Florijn ◽  
Roel Bijkerk ◽  
Nyika D. Kruyt ◽  
Anton Jan van Zonneveld ◽  
Marieke J. H. Wermer
Keyword(s):  
Ischemic Stroke ◽  
X Chromosome ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Transcriptional Level ◽  
Cell Type ◽  
Stroke Incidence ◽  
Secondary Damage ◽  
Mechanistic Understanding

Accumulating evidence pinpoints sex differences in stroke incidence, etiology and outcome. Therefore, more understanding of the sex-specific mechanisms that lead to ischemic stroke and aggravation of secondary damage after stroke is needed. Our current mechanistic understanding of cerebral ischemia states that endothelial quiescence in neurovascular units (NVUs) is a major physiological parameter affecting the cellular response to neuron, astrocyte and vascular smooth muscle cell (VSMC) injury. Although a hallmark of the response to injury in these cells is transcriptional activation, noncoding RNAs such as microRNAs exhibit cell-type and context dependent regulation of gene expression at the post-transcriptional level. This review assesses whether sex-specific microRNA expression (either derived from X-chromosome loci following incomplete X-chromosome inactivation or regulated by estrogen in their biogenesis) in these cells controls NVU quiescence, and as such, could differentiate stroke pathophysiology in women compared to men. Their adverse expression was found to decrease tight junction affinity in endothelial cells and activate VSMC proliferation, while their regulation of paracrine astrocyte signaling was shown to neutralize sex-specific apoptotic pathways in neurons. As such, these microRNAs have cell type-specific functions in astrocytes and vascular cells which act on one another, thereby affecting the cell viability of neurons. Furthermore, these microRNAs display actual and potential clinical implications as diagnostic and prognostic biomarkers in ischemic stroke and in predicting therapeutic response to antiplatelet therapy. In conclusion, this review improves the current mechanistic understanding of the molecular mechanisms leading to ischemic stroke in women and highlights the clinical promise of sex-specific microRNAs as novel diagnostic biomarkers for (silent) ischemic stroke.

scholarly journals Non-Coding RNAs in Pancreatic Cancer Diagnostics and Therapy: Focus on lncRNAs, circRNAs, and piRNAs

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4161
Author(s):  
Yiwei Li ◽  
Mohammed Najeeb Al Hallak ◽  
Philip A. Philip ◽  
Asfar S. Azmi ◽  
Ramzi M. Mohammad
Keyword(s):  
Pancreatic Cancer ◽  
High Mortality ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Regulation Of Gene Expression ◽  
Cancer Diagnostics ◽  
Circular Rnas ◽  
Diagnosis And Prognosis ◽  
Cellular Signal ◽  
Non Coding Rnas

Pancreatic cancer is an aggressive malignance with high mortality. The lack of early diagnosis and effective therapy contributes to the high mortality of this deadly disease. For a long time being, the alterations in coding RNAs have been considered as major targets for diagnosis and treatment of pancreatic cancer. However, with the advances in high-throughput next generation of sequencing more alterations in non-coding RNAs (ncRNAs) have been discovered in different cancers. Further mechanistic studies have demonstrated that ncRNAs such as long noncoding RNAs (lncRNA), circular RNAs (circRNA) and piwi-interacting RNA (piRNA) play vital roles in the regulation of tumorigenesis, tumor progression and prognosis. In recent years, increasing studies have focused on the roles of ncRNAs in the development and progression of pancreatic cancer. Novel findings have demonstrated that lncRNA, circRNA, and piRNA are critically involved in the regulation of gene expression and cellular signal transduction in pancreatic cancer. In this review, we summarize the current knowledge of roles of lncRNA, circRNA, and piRNA in the diagnosis and prognosis of pancreatic cancer, and molecular mechanisms underlying the regulation of these ncRNAs and related signaling in pancreatic cancer therapy. The information provided here will help to find new strategies for better treatment of pancreatic cancer.

scholarly journals Long Non-coding RNAs and MicroRNAs Interplay in Osteogenic Differentiation of Mesenchymal Stem Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Carmen Lanzillotti ◽  
Monica De Mattei ◽  
Chiara Mazziotta ◽  
Francesca Taraballi ◽  
John Charles Rotondo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Molecular Mechanisms ◽  
Bone Growth ◽  
Deep Understanding ◽  
Bone Diseases ◽  
Non Coding Rnas ◽  
Therapeutic Tools ◽  
Review Reports

Long non-coding RNAs (lncRNAs) have gained great attention as epigenetic regulators of gene expression in many tissues. Increasing evidence indicates that lncRNAs, together with microRNAs (miRNAs), play a pivotal role in osteogenesis. While miRNA action mechanism relies mainly on miRNA-mRNA interaction, resulting in suppressed expression, lncRNAs affect mRNA functionality through different activities, including interaction with miRNAs. Recent advances in RNA sequencing technology have improved knowledge into the molecular pathways regulated by the interaction of lncRNAs and miRNAs. This review reports on the recent knowledge of lncRNAs and miRNAs roles as key regulators of osteogenic differentiation. Specifically, we described herein the recent discoveries on lncRNA-miRNA crosstalk during the osteogenic differentiation of mesenchymal stem cells (MSCs) derived from bone marrow (BM), as well as from different other anatomical regions. The deep understanding of the connection between miRNAs and lncRNAs during the osteogenic differentiation will strongly improve knowledge into the molecular mechanisms of bone growth and development, ultimately leading to discover innovative diagnostic and therapeutic tools for osteogenic disorders and bone diseases.

scholarly journals The biological characteristics of transcription factors AP-2α and AP-2γ and their importance in various types of cancers

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Damian Kołat ◽  
Żaneta Kałuzińska ◽  
Andrzej K. Bednarek ◽  
Elżbieta Płuciennik
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Cancer Tissue ◽  
Diagnostic Biomarkers ◽  
Oncological Patients ◽  
Wide Range ◽  
Non Coding Rnas

Abstract The Activator Protein 2 (AP-2) transcription factor (TF) family is vital for the regulation of gene expression during early development as well as carcinogenesis process. The review focusses on the AP-2α and AP-2γ proteins and their dualistic regulation of gene expression in the process of carcinogenesis. Both AP-2α and AP-2γ influence a wide range of physiological or pathological processes by regulating different pathways and interacting with diverse molecules, i.e. other proteins, long non-coding RNAs (lncRNA) or miRNAs. This review summarizes the newest information about the biology of two, AP-2α and AP-2γ, TFs in the carcinogenesis process. We emphasize that these two proteins could have either oncogenic or suppressive characteristics depending on the type of cancer tissue or their interaction with specific molecules. They have also been found to contribute to resistance and sensitivity to chemotherapy in oncological patients. A better understanding of molecular network of AP-2 factors and other molecules may clarify the atypical molecular mechanisms occurring during carcinogenesis, and may assist in the recognition of new diagnostic biomarkers.

scholarly journals miR-155 Inhibits Expression of the MEF2A Protein to Repress Skeletal Muscle Differentiation

2011 ◽  
Vol 286 (41) ◽  
pp. 35339-35346 ◽  
Author(s):  
Hee Young Seok ◽  
Mariko Tatsuguchi ◽  
Thomas E. Callis ◽  
Aibin He ◽  
William T. Pu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Small Rnas ◽  
Myogenic Differentiation ◽  
Regulation Of Gene Expression ◽  
Myoblast Differentiation ◽  
Transcriptional Level ◽  
Muscle Gene Expression ◽  
Important Regulator ◽  
Non Coding Rnas ◽  
Muscle Gene

microRNAs (miRNAs) are 21–23-nucleotide non-coding RNAs. It has become more and more evident that this class of small RNAs plays critical roles in the regulation of gene expression at the post-transcriptional level. MEF2A is a member of the MEF2 (myogenic enhancer factor 2) family of transcription factors. Prior report showed that the 3′-untranslated region (3′-UTR) of the Mef2A gene mediated its repression; however, the molecular mechanism underlying this intriguing observation was unknown. Here, we report that MEF2A is repressed by miRNAs. We identify miR-155 as one of the primary miRNAs that significantly represses the expression of MEF2A. We show that knockdown of the Mef2A gene by siRNA impairs myoblast differentiation. Similarly, overexpression of miR-155 leads to the repression of endogenous MEF2A expression and the inhibition of myoblast differentiation. Most importantly, reintroduction of MEF2A in miR-155 overexpressed myoblasts was able to partially rescue the miR-155-induced myoblast differentiation defect. Our data therefore establish miR-155 as an important regulator of MEF2A expression and uncover its function in muscle gene expression and myogenic differentiation.

scholarly journals De novo profiling of long non-coding RNAs involved in MC-LR–induced liver injury in whitefish: discovery and perspectives

2020 ◽  
Author(s):  
Maciej Florczyk ◽  
Paweł Brzuzan ◽  
Maciej Woźny
Keyword(s):  
Liver Injury ◽  
Molecular Mechanisms ◽  
Liver Toxicity ◽  
De Novo ◽  
Sequence Data ◽  
Regulation Of Gene Expression ◽  
Model Organisms ◽  
Coregonus Lavaretus ◽  
Digital Repository ◽  
Non Coding Rnas

Abstract BackgroundMicrocystin-LR (MC-LR) is a potent hepatotoxin for which a substantial gap in knowledge persists regarding the underlying molecular mechanisms of liver toxicity and injury. Although long non-coding RNAs (lncRNAs) have been extensively studied in model organisms, and their roles have been identified in various cellular processes including participation in regulation of gene expression together with microRNAs, our knowledge concerning the role of lncRNAs in liver injury is limited even in mammals. Given that lncRNAs show low levels of sequence conservation, their role becomes even more unclear in non-model organisms without an annotated genome, like whitefish (Coregonus lavaretus). The objective of this study was to discover and profile aberrantly expressed polyadenylated lncRNAs that are involved in MC-LR–induced liver injury in whitefish.ResultsUsing polyA-enriched RNA-Seq data, we de novo assembled a high quality whitefish liver transcriptome. This enabled us to find 94 differentially expressed (DE) putative evolutionary-conserved lncRNAs (orthologous to known lncRNAs in other species), such as MALAT1, HOTTIP, HOTAIR or HULC and 4,429 DE putative novel whitefish lncRNAs, which differed from annotated protein-coding transcripts (PCTs) in terms of minimum free energy, GC base-pair content and length. Additionally, we identified DE non-coding transcripts that might be 3’ autonomous untranslated regions of mRNAs (3’UTRs). We found that, in response to MC-LR treatment, these potential 3’UTRs could either be coexpressed with PCTs from the same mRNA, or the 3’UTRs were upregulated while the corresponding PCTs were downregulated, suggesting 3’UTR-dependent gene regulation.ConclusionsTo our knowledge this is the first report on aberrantly expressed lncRNAs in MC-LR–induced liver injury in whitefish. We found both evolutionary conserved lncRNAs as well as novel whitefish lncRNAs that could serve as biomarkers of severe and chronic liver injury. The lncRNA sequence data files and raw sequence files are available in the Dryad Digital Repository and the NCBI Sequence Read Archive, respectively.

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