Mechanisms and Functions of Long Non-Coding RNAs at Multiple Regulatory Levels

Zhang, Xiaopei; Wang, Wei; Zhu, Weidong; Dong, Jie; Cheng, Yingying; Yin, Zujun; Shen, Fafu

doi:10.3390/ijms20225573

Cited by 621 publications

(462 citation statements)

References 125 publications

(140 reference statements)

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“…Since then, aberrant lncRNA-MIAT has been reported to be associated with microvascluar dysfunction, diabetic retinopathy and coronary atherosclerotic heart diseases (Yan et al, 2015;Li et al, 2018;Tan et al, 2019). LncRNA-mediated regulation of gene expression involves a variety of mechanisms that include sequestration of transcription factors, activation of transcription of certain genes, and binding to complementary microRNAs via base pairing to sequester them (Peng et al, 2017;Zhang et al, 2019;Zhou et al, 2019;Wang et al, 2020). Recently, it is well-documented that lncRNAs can influence mRNA levels by Tissue homogenate of mice heart with above-mentioned treatments were collected and processed for western blotting to examine the protein expression of IL-17, IL-1β, TNF-α, IL-6, collagen I, and collagen III, respectively, as Figure 2B mentioned.…”

Section: Discussionmentioning

confidence: 99%

LncRNA-MIAT-Mediated miR-214-3p Silencing Is Responsible for IL-17 Production and Cardiac Fibrosis in Diabetic Cardiomyopathy

Mai

et al. 2020

Front. Cell Dev. Biol.

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As an important complication of diabetes mellitus, diabetic cardiomyopathy (DCM) is characterized by a silent development in its earlier stage and a deficient cardiomyocyte contractility in its late stage. So far, little advance has been achieved to reverse this pathological change. LncRNAs are defined as a large cluster of RNAs without the function of encoding proteins, but have the capacity in controlling gene expression. Interleukin-17 (IL-17), a proinflammatory cytokine, is a key regulator of host inflammation. Clinically, it plays a crucial role in the pathogenesis of cardiac interstitial fibrosis. In this study, we reported that high glucose-induced lncRNA-MIAT upregulation is responsible for proinflammatory IL-17 production in cardiomyocytes. The underlying mechanism is likely due to that lncRNA-MIAT specific attenuates miR-214-3p-mediated inhibitory effect on IL-17 expression. As a result, attenuated IL-17 expression significantly ameliorate cardiac fibrosis, followed by improvement of cardiac contractility. Taken together, our study first suggests that lncRNA-MIAT plays a key role in DCM and targeting lncRNA-MIAT may become a potential strategy to treat DCM.

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Section: Discussionmentioning

confidence: 99%

LncRNA-MIAT-Mediated miR-214-3p Silencing Is Responsible for IL-17 Production and Cardiac Fibrosis in Diabetic Cardiomyopathy

Mai

et al. 2020

Front. Cell Dev. Biol.

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“…Epigenetic regulation is increasingly recognized to be important during plant germline development [129]. While long non-coding RNAs can act in modulating DNA methylation and histone modifications to regulate gene activity [130], future investigations are required to elucidate their specific importance during reproductive development in detail.…”

Section: Epigenetic Regulatory Pathways Are Involved In Regulation Ofmentioning

confidence: 99%

Controlling Apomixis: Shared Features and Distinct Characteristics of Gene Regulation

Schmidt

2020

Genes

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In higher plants, sexual and asexual reproduction through seeds (apomixis) have evolved as alternative strategies. As apomixis leads to the formation of clonal offspring, its great potential for agricultural applications has long been recognized. However, the genetic basis and the molecular control underlying apomixis and its evolutionary origin are to date not fully understood. Both in sexual and apomictic plants, reproduction is tightly controlled by versatile mechanisms regulating gene expression, translation, and protein abundance and activity. Increasing evidence suggests that interrelated pathways including epigenetic regulation, cell-cycle control, hormonal pathways, and signal transduction processes are relevant for apomixis. Additional molecular mechanisms are being identified that involve the activity of DNA- and RNA-binding proteins, such as RNA helicases which are increasingly recognized as important regulators of reproduction. Together with other factors including non-coding RNAs, their association with ribosomes is likely to be relevant for the formation and specification of the apomictic reproductive lineage. Subsequent seed formation appears to involve an interplay of transcriptional activation and repression of developmental programs by epigenetic regulatory mechanisms. In this review, insights into the genetic basis and molecular control of apomixis are presented, also taking into account potential relations to environmental stress, and considering aspects of evolution.

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“…Most of them are transcribed by polymerase II. LncRNAs are associated with the regulations of numerous cellular processes in mammals, such as chromatin remodeling, chromatin modification, dosage compensation effect, genomic imprinting, and others [59]. These molecules do not act by themselves, but form complexes and execute their regulatory functions through interacting with proteins.…”

Section: Long Non-coding Rnasmentioning

confidence: 99%

“…They also are able to regulate the transcription by the interaction with transcriptional factors. The implication of lncRNAs in post-transcriptional regulation is based on their ability to interact with splicing factors and proteins and subsequently regulate mRNA alternative splicing, and splicing factors can also directly regulate lncRNA alternative splicing [59].…”

Section: Long Non-coding Rnasmentioning

confidence: 99%

In Search for Genes Related to Atherosclerosis and Dyslipidemia Using Animal Models

Poznyak

Grechko

Wetzker

et al. 2020

IJMS

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Atherosclerosis is a multifactorial chronic disease that affects large arteries and may lead to fatal consequences. According to current understanding, inflammation and lipid accumulation are the two key mechanisms of atherosclerosis development. Animal models based on genetically modified mice have been developed to investigate these aspects. One such model is low-density lipoprotein (LDL) receptor knockout (KO) mice (ldlr −/− ), which are characterized by a moderate increase of plasma LDL cholesterol levels. Another widely used genetically modified mouse strain is apolipoprotein-E KO mice (apoE −/− ) that lacks the primary lipoprotein required for the uptake of lipoproteins through the hepatic receptors, leading to even greater plasma cholesterol increase than in ldlr −/− mice. These and other animal models allowed for conducting genetic studies, such as genome-wide association studies, microarrays, and genotyping methods, which helped identifying more than 100 mutations that contribute to atherosclerosis development. However, translation of the results obtained in animal models for human situations was slow and challenging. At the same time, genetic studies conducted in humans were limited by low sample sizes and high heterogeneity in predictive subclinical phenotypes. In this review, we summarize the current knowledge on the use of KO mice for identification of genes implicated in atherosclerosis and provide a list of genes involved in atherosclerosis-associated inflammatory pathways and their brief characteristics. Moreover, we discuss the approaches for candidate gene search in animals and humans and discuss the progress made in the field of epigenetic studies that appear to be promising for identification of novel biomarkers and therapeutic targets.challenge is the lack of effective treatment approaches, which is the consequence of our incomplete understanding of the processes that underlie the pathogenesis. Genetic base is one of the most important features that are involved in the disease development.Currently, the most widely used anti-atherosclerosis drugs are statins [3]. The aim of statin therapy is reducing the blood level of low-density lipoprotein (LDL) cholesterol, which is a well-known pro-atherogenic agent. It was demonstrated that statin therapy reduces the risk of cardiovascular events by approximately one third [4]. However, statin therapy alone cannot be regarded as effective treatment of atherosclerosis. Increasing the plasma levels of high-density lipoprotein (HDL), which has anti-atherogenic properties, is another promising approach. Accumulating evidence shows that high levels of HDL cholesterol can inhibit atherosclerosis progression. To date, several therapeutic agents that increase HDL levels are known, including niacin, fibrates, and statins. Among the recently developed medications are apoA-I-phospholipid complexes, human apoA-I and apoA-I-mimetic peptides, and inhibitors of cholesterol ester transfer protein, which have reached the level of clinical trials. However, the inhibitor ...

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Mechanisms and Functions of Long Non-Coding RNAs at Multiple Regulatory Levels

Cited by 621 publications

References 125 publications

LncRNA-MIAT-Mediated miR-214-3p Silencing Is Responsible for IL-17 Production and Cardiac Fibrosis in Diabetic Cardiomyopathy

LncRNA-MIAT-Mediated miR-214-3p Silencing Is Responsible for IL-17 Production and Cardiac Fibrosis in Diabetic Cardiomyopathy

Controlling Apomixis: Shared Features and Distinct Characteristics of Gene Regulation

In Search for Genes Related to Atherosclerosis and Dyslipidemia Using Animal Models

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