Abstract:MicroRNAs (miRNAs and miRs) are a large class of noncoding, single-stranded, small RNA molecules. The precise control of their expression is essential for keeping tissue homeostasis and normal development of organisms. Thus, unbalanced expression of miRNAs is a hallmark of many diseases. Two to dozens of miRNAs can form into a miRNA cluster, and the miR-17-92 cluster is one of them. Although firstly described as an oncogenic miRNA cluster, the miR-17-92 cluster has also been found to play critical role in norm… Show more
“…miR‐143/145 cluster is important for vascular smooth muscle cell functions such as migration, plasticity and contractile ability (Song & Li, ). Both cardiac cell development and differentiation are regulated by miR‐17/92 cluster (Gu et al, ). miRNA clusters associated with cardiac development and regeneration include miR‐1/133a clusters (Liu et al, ).…”
Section: Significance Of Mirna Clusters In Health and Diseasementioning
MicroRNAs (miRNAs) are endogenous, small non-coding RNAs known to regulate expression of protein-coding genes. A large proportion of miRNAs are highly conserved, localized as clusters in the genome, transcribed together from physically adjacent miRNAs and show similar expression profiles. Since a single miRNA can target multiple genes and miRNA clusters contain multiple miRNAs, it is important to understand their regulation, effects and various biological functions. Like protein-coding genes, miRNA clusters are also regulated by genetic and epigenetic events. These clusters can potentially regulate every aspect of cellular function including growth, proliferation, differentiation, development, metabolism, infection, immunity, cell death, organellar biogenesis, messenger signalling, DNA repair and self-renewal, among others. Dysregulation of miRNA clusters leading to altered biological functions is key to the pathogenesis of many diseases including carcinogenesis. Here, we review recent advances in miRNA cluster research and discuss their regulation and biological functions in pathological conditions.
“…miR‐143/145 cluster is important for vascular smooth muscle cell functions such as migration, plasticity and contractile ability (Song & Li, ). Both cardiac cell development and differentiation are regulated by miR‐17/92 cluster (Gu et al, ). miRNA clusters associated with cardiac development and regeneration include miR‐1/133a clusters (Liu et al, ).…”
Section: Significance Of Mirna Clusters In Health and Diseasementioning
MicroRNAs (miRNAs) are endogenous, small non-coding RNAs known to regulate expression of protein-coding genes. A large proportion of miRNAs are highly conserved, localized as clusters in the genome, transcribed together from physically adjacent miRNAs and show similar expression profiles. Since a single miRNA can target multiple genes and miRNA clusters contain multiple miRNAs, it is important to understand their regulation, effects and various biological functions. Like protein-coding genes, miRNA clusters are also regulated by genetic and epigenetic events. These clusters can potentially regulate every aspect of cellular function including growth, proliferation, differentiation, development, metabolism, infection, immunity, cell death, organellar biogenesis, messenger signalling, DNA repair and self-renewal, among others. Dysregulation of miRNA clusters leading to altered biological functions is key to the pathogenesis of many diseases including carcinogenesis. Here, we review recent advances in miRNA cluster research and discuss their regulation and biological functions in pathological conditions.
“…MiRNAs participate in normal cellular physiology such as differentiation and proliferation but also in the progression of a variety of diseases by influencing gene expression in heart, lung, immune system, etc. [37]. Both miRNA biosynthesis and function have been extensively reviewed [38,39].…”
Section: Circulating Mirnas As Biomarkers In Cardiovascular Diseasesmentioning
confidence: 99%
“…In addition, a large proportion of miRNAs are expressed as clusters that are subsequently processed into individual mature molecules. It has been demonstrated that specific miRNA clusters are essential to the normal development of the cardiovascular system [37]. For example, some miRNAs clusters are important for activation of endothelial cells, post-natal neovascularization, cardiovascular development and regeneration [37,46] as well as for vascular smooth muscle cell functions such as migration, plasticity, and contractile ability [47].…”
Section: Circulating Mirnas As Biomarkers In Cardiovascular Diseasesmentioning
Micro-RNAs (miRNAs) play a pivotal role in the development and physiology of the cardiovascular system while they have been associated with multiple cardiovascular diseases (CVDs). Several cardiac miRNAs are detectable in circulation (circulating miRNAs; c-miRNAs) and are emerging as diagnostic and therapeutic biomarkers for CVDs. c-miRNAs exhibit numerous essential characteristics of biomarkers while they are extremely stable in circulation, their expression is tissue-/disease-specific, and they can be easily detected using sequence-specific amplification methods. These features of c-miRNAs are helpful in the development of non-invasive assays to monitor the progress of CVDs. Despite significant progress in the detection of c-miRNAs in serum and plasma, there are many contradictory publications on the alterations of cardiac c-miRNAs concentration in circulation. The aim of this review is to examine the pre-analytical and analytical factors affecting the quantification of c-miRNAs and provide general guidelines to increase the accuracy of the diagnostic tests in order to improve future research on cardiac c-miRNAs.
“…Importantly, we identified epigenetic alterations as a consequence of gestational CRD which support the phenotypes observed. The promoter region of miR17-92, required for heart and bone development (Gu et al 2017;Mohan et al 2015), was hypermethylated in the jet lag offspring, and increased expression of one of the targets of this miR cluster, P21, was increased in the hearts of the jet lag offspring. Additionally, DMRs were identified within circadian clock genes and genes involved in clock resetting, resulting in altered gene expression.…”
Section: Discussionmentioning
confidence: 98%
“…We performed gene ontology analysis using this group of differentially methylated genes and identified biological processes which are affected in the jet lag offspring (Figure 4b,c). A feature that all these processes have in common is that they are regulated by micro-RNA cluster miR17-92 (Gu et al 2017;Mendell 2008;Mohan et al 2015), which is hypermethylated in the DEL and ADV groups (Figure 4a). A graphic representation of the methylation levels in miR17 is shown in Figure S4A.…”
Section: Chronic Gestational Jet Lag Affects Heart Morphology and Funmentioning
Circadian rhythm disturbance (CRD) increases the risk of disease, e.g. metabolic syndrome, cardiovascular disease, and cancer. In the present study, we investigated later life adverse health effects triggered by repeated jet lag during gestation. Pregnant mice were subjected to a regular light-dark cycle (CTRL) or to a repeated delay (DEL) or advance (ADV) jet lag protocol. Both DEL and ADV offspring showed reduced weight gain. ADV offspring had an increased circadian period, and an altered response to a jet lag was observed in both DEL and ADV offspring. Analysis of the bones of adult male ADV offspring revealed reduced cortical bone mass and strength. Strikingly, analysis of the heart identified structural abnormalities and impaired heart function. Finally, DNA methylation analysis revealed hypermethylation of miR17-92 cluster and differential methylation within circadian clock genes, which correlated with altered gene expression. We show that developmental CRD affects the circadian system and predisposes to non-communicable disease in adult life.
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