scholarly journals Novel Insights Linking lncRNAs and Metabolism With Implications for Cardiac Regeneration

2021 ◽  
Vol 12 ◽  
Author(s):  
Magda Correia ◽  
Bruno Bernardes de Jesus ◽  
Sandrina Nóbrega-Pereira
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Metabolic Pathways ◽  
Cardiac Regeneration ◽  
Developed Countries ◽  
Anaerobic Glycolysis ◽  
Metabolic Signaling ◽  
Master Regulators ◽  
Carbohydrate And Lipid Metabolism ◽  
Non Coding Rnas

Heart disease is the leading cause of mortality in developed countries. The associated pathology is typically characterized by the loss of cardiomyocytes that leads, eventually, to heart failure. Although conventional treatments exist, novel regenerative procedures are warranted for improving cardiac regeneration and patients well fare. Whereas following injury the capacity for regeneration of adult mammalian heart is limited, the neonatal heart is capable of substantial regeneration but this capacity is lost at postnatal stages. Interestingly, this is accompanied by a shift in the metabolic pathways and energetic fuels preferentially used by cardiomyocytes from embryonic glucose-driven anaerobic glycolysis to adult oxidation of substrates in the mitochondria. Apart from energetic sources, metabolites are emerging as key regulators of gene expression and epigenetic programs which could impact cardiac regeneration. Long non-coding RNAs (lncRNAs) are known master regulators of cellular and organismal carbohydrate and lipid metabolism and play multifaceted functions in the cardiovascular system. Still, our understanding of the metabolic determinants and pathways that can promote cardiac regeneration in the injured hearth remains limited. Here, we will discuss the emerging concepts that provide evidence for a molecular interplay between lncRNAs and metabolic signaling in cardiovascular function and whether exploiting this axis could provide ground for improved regenerative strategies in the heart.

Abstract 286: Long Noncoding RNAs Are Differentially Expressed in Heart Failure

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Emma L Robinson ◽  
Syed Haider ◽  
Hillary Hei ◽  
Richard T Lee ◽  
Roger S Foo
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Significant Proportion ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Control Of Gene Expression ◽  
Failing Heart ◽  
Novel Transcripts ◽  
Non Coding Rnas

Heart failure comprises of clinically distinct inciting causes but a consistent pattern of change in myocardial gene expression supports the hypothesis that unifying biochemical mechanisms underlie disease progression. The recent RNA-seq revolution has enabled whole transcriptome profiling, using deep-sequencing technologies. Up to 70% of the genome is now known to be transcribed into RNA, a significant proportion of which is long non-coding RNAs (lncRNAs), defined as polyribonucleotides of ≥200 nucleotides. This project aims to discover whether the myocardium expression of lncRNAs changes in the failing heart. Paired end RNA-seq from a 300-400bp library of ‘stretched’ mouse myocyte total RNA was carried out to generate 76-mer sequence reads. Mechanically stretching myocytes with equibiaxial stretch apparatus mimics pathological hypertrophy in the heart. Transcripts were assembled and aligned to reference genome mm9 (UCSC), abundance determined and differential expression of novel transcripts and alternative splice variants were compared with that of control (non-stretched) mouse myocytes. Five novel transcripts have been identified in our RNA-seq that are differentially expressed in stretched myocytes compared with non-stretched. These are regions of the genome that are currently unannotated and potentially are transcribed into non-coding RNAs. Roles of known lncRNAs include control of gene expression, either by direct interaction with complementary regions of the genome or association with chromatin remodelling complexes which act on the epigenome.Changes in expression of genes which contribute to the deterioration of the failing heart could be due to the actions of these novel lncRNAs, immediately suggesting a target for new pharmaceuticals. Changes in the expression of these novel transcripts will be validated in a larger sample size of stretched myocytes vs non-stretched myocytes as well as in the hearts of transverse aortic constriction (TAC) mice vs Sham (surgical procedure without the aortic banding). In vivo investigations will then be carried out, using siLNA antisense technology to silence novel lncRNAs in mice.

scholarly journals Non-coding RNAs in Cardiac Regeneration

2021 ◽  
Vol 12 ◽  
Author(s):  
Ting Yuan ◽  
Jaya Krishnan
Keyword(s):  
Heart Failure ◽  
Cardiac Tissue ◽  
Cardiac Regeneration ◽  
Circular Rnas ◽  
Great Promise ◽  
Cardiomyocyte Proliferation ◽  
Non Coding Rnas ◽  
Key Aspects

The adult heart has a limited capacity to replace or regenerate damaged cardiac tissue following severe myocardial injury. Thus, therapies facilitating the induction of cardiac regeneration holds great promise for the treatment of end-stage heart failure, and for pathologies invoking severe cardiac dysfunction as a result of cardiomyocyte death. Recently, a number of studies have demonstrated that cardiac regeneration can be achieved through modulation and/or reprogramming of cardiomyocyte proliferation, differentiation, and survival signaling. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), are reported to play critical roles in regulating key aspects of cardiomyocyte physiologic and pathologic signaling, including the regulation of cardiac regeneration both in vitro and in vivo. In this review, we will explore and detail the current understanding of ncRNA function in cardiac regeneration, and highlight established and novel strategies for the treatment of heart failure through modulation of ncRNAs-driven cardiac regeneration.

scholarly journals Hypoxia-Induced Non-Coding RNAs Controlling Cell Viability in Cancer

2021 ◽  
Vol 22 (4) ◽  
pp. 1857
Author(s):  
Maria Magdalena Barreca ◽  
Chiara Zichittella ◽  
Riccardo Alessandro ◽  
Alice Conigliaro
Keyword(s):  
Gene Expression ◽  
Cancer Progression ◽  
Biological Activities ◽  
Tumour Microenvironment ◽  
Cell Phenotype ◽  
Low Oxygen ◽  
Master Regulators ◽  
Signalling Transduction ◽  
Non Coding Rnas ◽  
Multiple Levels

Hypoxia, a characteristic of the tumour microenvironment, plays a crucial role in cancer progression and therapeutic response. The hypoxia-inducible factors (HIF-1α, HIF-2α, and HIF-3α), are the master regulators in response to low oxygen partial pressure, modulating hypoxic gene expression and signalling transduction pathways. HIFs’ activation is sufficient to change the cell phenotype at multiple levels, by modulating several biological activities from metabolism to the cell cycle and providing the cell with new characteristics that make it more aggressive. In the past few decades, growing numbers of studies have revealed the importance of non-coding RNAs (ncRNAs) as molecular mediators in the establishment of hypoxic response, playing important roles in regulating hypoxic gene expression at the transcriptional, post-transcriptional, translational, and posttranslational levels. Here, we review recent findings on the different roles of hypoxia-induced ncRNAs in cancer focusing on the data that revealed their involvement in tumour growth.

Real world heart failure epidemiology and outcome: a population-based analysis of 1,990,162 heart failure patients

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Leszek ◽  
M Zaleska-Kociecka ◽  
D Was ◽  
K Witczak ◽  
K Bartolik ◽  
...  
Keyword(s):  
Heart Failure ◽  
Real World ◽  
Age Groups ◽  
Developed Countries ◽  
Funding Source ◽  
Newly Diagnosed ◽  
The European Union ◽  
Ministry Of Health ◽  
The Real ◽  
Incidence Prevalence

Abstract Background Heart failure (HF) is the leading cause of death and hospitalization in developed countries. Most of the information about HF is based on selected cohorts, the real epidemiology of HF is scarce. Purpose To assess trends in the real world incidence, prevalence and mortality of all in-and outpatients with HF who presented in public health system in 2009–2018 in Poland. Methods It is a retrospective analysis of 1,990,162 patients who presented with HF in Poland in years 2009–2018. It is a part of nationwide Polish Ministry of Health registry that collects detailed information for the entire Polish population (38,495,659 in 2013) since 2009. Detailed data within the registry were collected since 2013. HF was recorded if HF diagnosis was coded (ICD-10). Results The incidence of HF in Poland fell down from 2013 to reach 127,036 newly diagnosed cases (330 per 100,000 population) in 2018 that equals to 43.6% drop. This decrease was mainly driven by marked reduction in females (p<0.001; Fig. 1A) and HF of ischaemic etiology (HF-IE vs HF-nonIE, Fig. 1B. p<0.001). The HF incidence per 100,000 population decreased across all age groups with the greatest drop in the youngest (Table 1). The prevalence rose by 11.6% to reach 1,242,129 (3233 per 100,000 population) in 2018 with significantly greater increase in females and HF-IE (both p<0.0001, Fig. 1C and D, respectively). The HF prevalence per 100,000 population increased across all age groups except for the 70–79 years old. (Table 1). Mortality increased by 28.5% to reach 142,379 cases (370 per 100,000 population) in 2018. The rise was more pronounced among females (p=0.015, Fig. 1E) and in HF-IE (p<0.001, Fig. 1F). The HF mortality per 100 000 population increased across all age groups, except for the 50–59 subgroup (Table 1). Conclusions Heart failure incidence plummeted in years 2013–2018 in Poland due to drop in newly diagnosed HF-IE. Despite that fact, the prevalence and mortality increased with rising trends in HF-IE. Figure 1. Incidence, prevalence, mortality trends Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): The project is co-financed by the European Union from the European Social Fund under the Operational Programme Knowledge Education Development and it is being carried out by the Analyses and Strategies Department of the Polish Ministry of Health

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.

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