FEASIBILITY OF THE NON-CODING RNA GRADIENTS IN CELLS

In eukaryotic cells, the gene transcription often results in the formation of non-coding RNAs (ncRNAs). The key function of such RNAs is to bind to and modulate the activity of mRNAs and/or proteins. To scrutinize this ncRNA function in a cell, the author (i) proposes a spatio-temporal kinetic model, including ncRNA–protein association and degradation, (ii) derives a criterion of feasibility of the ncRNA gradients, and (iii) shows that this criterion can be satisfied with physically reasonable values of the model parameters. Thus, the ncRNA gradients are feasible. For the ncRNA–mRNA association and degradation, the situation is similar. The likely biological role of such gradients is open for debate.

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Emerging role of a novel small non-coding regulatory RNA: tRNA-derived small RNA

ExRNA ◽

10.1186/s41544-019-0036-7 ◽

2019 ◽

Vol 1 (1) ◽

Author(s):

Fangfang Jin ◽

Zhigang Guo

Keyword(s):

Small Rna ◽

Current Knowledge ◽

Future Research ◽

Regulatory Rna ◽

Biological Functions ◽

Research Directions ◽

Non Coding Rna ◽

Future Research Directions ◽

Non Coding Rnas

Abstract The discovery of small non-coding RNAs, such as miRNA and piRNA, has dramatically changed our understanding of the role RNA plays in organisms. Recent studies show that a novel small non-coding RNA generated from cleavage of tRNA or pre-tRNA, called tRNA-derived small RNA (tsRNA), serves as a new regulator of gene expression. tsRNA has been determined participate in regulating some specific physiological and pathological processes. Although knowledge regarding the biological roles of miRNA and piRNA is expanding, whether tsRNAs play similar roles remains poorly understood. Here, we review the current knowledge regarding the mechanisms of action and biological functions of tsRNAs in intracellular, extracellular and intergenerational inheritance, and highlight the potential application of tsRNAs in human diseases, and present the current problems and future research directions.

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Long Non-coding RNA XIST Attenuates Diabetic Peripheral Neuropathy by Inducing Autophagy Through MicroRNA-30d-5p/sirtuin1 Axis

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.655157 ◽

2021 ◽

Vol 8 ◽

Author(s):

Bei-Yan Liu ◽

Lin Li ◽

Li-Wei Bai ◽

Chang-Shui Xu

Keyword(s):

Oxidative Stress ◽

Peripheral Neuropathy ◽

Schwann Cells ◽

Diabetic Peripheral Neuropathy ◽

Beclin 1 ◽

Diabetic Mice ◽

Non Coding Rna ◽

Non Coding Rnas ◽

Long Non Coding Rna

Diabetic peripheral neuropathy (DPN) is a prevalent diabetes mellitus (Feldman et al., 2017) complication and the primary reason for amputation. Meanwhile, long non-coding RNAs (lncRNAs) are a type of regulatory non-coding RNAs (ncRNAs) that broadly participate in DPN development. However, the correlation of lncRNA X-inactive specific transcript (XIST) with DPN remains unclear. In this study, we were interested in the role of XIST in the modulation of DPN progression. Significantly, our data showed that the expression of XIST and sirtuin1 (SIRT1) was inhibited, and the expression of microRNA-30d-5p (miR-30d-5p) was enhanced in the trigeminal sensory neurons of the diabetic mice compared with the normal mice. The levels of LC3II and Beclin-1 were inhibited in the diabetic mice. The treatment of high glucose (HG) reduced the XIST expression in Schwann cells. The apoptosis of Schwann cells was enhanced in the HG-treated cells, but the overexpression of XIST could block the effect in the cells. Moreover, the levels of LC3II and Beclin-1 were reduced in the HG-treated Schwann cells, while the overexpression of XIST was able to reverse this effect. The HG treatment promoted the production of oxidative stress, while the XIST overexpression could attenuate this result in the Schwann cells. Mechanically, XIST was able to sponge miR-30d-5p and miR-30d-5p-targeted SIRT1 in the Schwann cells. MiR-30d-5p inhibited autophagy and promoted oxidative stress in the HG-treated Schwann cells, and SIRT1 presented a reversed effect. MiR-30d-5p mimic or SIRT1 depletion could reverse XIST overexpression-mediated apoptosis and autophagy of the Schwann cells. Thus, we concluded that XIST attenuated DPN by inducing autophagy through miR-30d-5p/SIRT1 axis. XIST and miR-30d-5p may be applied as the potential targets for DPN therapy.

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Long non-coding RNA ARAP1-AS1 accelerates cell proliferation and migration in breast cancer through miR-2110/HDAC2/PLIN1 axis

Bioscience Reports ◽

10.1042/bsr20191764 ◽

2020 ◽

Vol 40 (4) ◽

Cited By ~ 1

Author(s):

Chong Lu ◽

Xiuhua Wang ◽

Xiangwang Zhao ◽

Yue Xin ◽

Chunping Liu

Keyword(s):

Breast Cancer ◽

Normal Breast ◽

Tumor Promoter ◽

Women Health ◽

Non Coding Rna ◽

Non Coding Rnas ◽

And Migration ◽

Breast Tissues ◽

Long Non Coding Rna

Abstract Breast cancer (BC) poses a great threaten to women health. Numerous evidences suggest the important role of long non-coding RNAs (lncRNAs) in BC development. In the present study, we intended to investigate the role of ARAP1-AS1 in BC progression. First of all, the GEPIA data suggested that ARAP1-AS1 was highly expressed in breast invasive carcinoma (BRAC) tissues compared with the normal breast tissues. Meanwhile, the expression of ARAP1-AS1 was greatly up-regulated in BC cell lines. ARAP1-AS1 knockdown led to repressed proliferation, strengthened apoptosis and blocked migration of BC cells. Moreover, ARAP1-AS1 could boost HDAC2 expression in BC through sponging miR-2110 via a ceRNA mechanism. Of note, the UCSC predicted that HDAC2 was a potential transcriptional regulator of PLIN1, an identified tumor suppressor in BC progression. Moreover, we explained that the repression of HDAC2 on PLIN1 was owing to its deacetylation on PLIN1 promoter. More importantly, depletion of PLIN1 attenuated the mitigation function of ARAP1-AS1 silence on the malignant phenotypes of BC cells. To sum up, ARAP1-AS1 serves a tumor-promoter in BC development through modulating miR-2110/HDAC2/PLIN1 axis, which may help to develop novel effective targets for BC treatment.

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The Long Non-Coding RNA H19 Drives the Proliferation of Diffuse Intrinsic Pontine Glioma with H3K27 Mutation

International Journal of Molecular Sciences ◽

10.3390/ijms22179165 ◽

2021 ◽

Vol 22 (17) ◽

pp. 9165

Author(s):

David Roig-Carles ◽

Holly Jackson ◽

Katie F. Loveson ◽

Alan Mackay ◽

Rebecca L. Mather ◽

...

Keyword(s):

Large Family ◽

Diffuse Intrinsic Pontine Glioma ◽

Locked Nucleic Acid ◽

Normal Brain ◽

Pontine Glioma ◽

Incurable Cancer ◽

Non Coding Rna ◽

Non Coding Rnas ◽

Long Non Coding Rna

Diffuse intrinsic pontine glioma (DIPG) is an incurable paediatric malignancy. Identifying the molecular drivers of DIPG progression is of the utmost importance. Long non-coding RNAs (lncRNAs) represent a large family of disease- and tissue-specific transcripts, whose functions have not yet been elucidated in DIPG. Herein, we studied the oncogenic role of the development-associated H19 lncRNA in DIPG. Bioinformatic analyses of clinical datasets were used to measure the expression of H19 lncRNA in paediatric high-grade gliomas (pedHGGs). The expression and sub-cellular location of H19 lncRNA were validated in DIPG cell lines. Locked nucleic acid antisense oligonucleotides were designed to test the function of H19 in DIPG cells. We found that H19 expression was higher in DIPG vs. normal brain tissue and other pedHGGs. H19 knockdown resulted in decreased cell proliferation and survival in DIPG cells. Mechanistically, H19 buffers let-7 microRNAs, resulting in the up-regulation of oncogenic let-7 target (e.g., SULF2 and OSMR). H19 is the first functionally characterized lncRNA in DIPG and a promising therapeutic candidate for treating this incurable cancer.

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Long Non-Coding RNAs as Endogenous Target Mimics and Exploration of Their Role in Low Nutrient Stress Tolerance in Plants

Genes ◽

10.3390/genes9090459 ◽

2018 ◽

Vol 9 (9) ◽

pp. 459 ◽

Cited By ~ 5

Author(s):

Priyanka Borah ◽

Antara Das ◽

Matthew Milner ◽

Arif Ali ◽

Alison Bentley ◽

...

Keyword(s):

Gene Regulation ◽

Next Generation Sequencing ◽

Non Coding Rna ◽

Genome Wide ◽

Non Coding Rnas ◽

Endogenous Target ◽

Long Non Coding Rna ◽

Nutrient Homeostasis ◽

Generation Sequencing

Long non-coding RNA (lncRNA) research in plants has recently gained momentum taking cues from studies in animals systems. The availability of next-generation sequencing has enabled genome-wide identification of lncRNA in several plant species. Some lncRNAs are inhibitors of microRNA expression and have a function known as target mimicry with the sequestered transcript known as an endogenous target mimic (eTM). The lncRNAs identified to date show diverse mechanisms of gene regulation, most of which remain poorly understood. In this review, we discuss the role of identified putative lncRNAs that may act as eTMs for nutrient-responsive microRNAs (miRNAs) in plants. If functionally validated, these putative lncRNAs would enhance current understanding of the role of lncRNAs in nutrient homeostasis in plants.

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Long non-coding RNA MEG3 silencing and microRNA-214 restoration elevate osteoprotegerin expression to ameliorate osteoporosis by limiting TXNIP

10.21203/rs.2.19130/v1 ◽

2019 ◽

Author(s):

Rui Ding ◽

ZhengTao Gu ◽

ChangSheng Yang ◽

CaiQiang Huang ◽

QingChu Li ◽

...

Keyword(s):

Interacting Protein ◽

Blood Samples ◽

Rat Models ◽

Thioredoxin Interacting Protein ◽

Non Coding Rna ◽

Proliferation And Differentiation ◽

Non Coding Rnas ◽

Long Non Coding Rna ◽

Rat Osteoblasts

Abstract BackgroundLong non-coding RNAs (LncRNAs) have been found to regulate innumerable diseases, yet the role of lncRNA MEG3 in osteoporosis (OP) has rarely been discussed. Here, we intend to probe into the mechanism of MEG3 on OP development by modulating microRNA-214 (miR-214) and thioredoxin-interacting protein (TXNIP)MethodsRat models of OP were established. MEG3, miR-214, and TXNIP mRNA expression in rat femoral tissues was detected, along with TXNIP, PCNA, cyclin D1, OCN, RUNX2, Osteolix, OPG, and PANKL protein expression. Ca, P and ALP contents in rat blood samples were also determined. Primary osteoblasts were isolated and cultured. Viability, COL-I, COL-II and COL-Χ contents, ALP content and activity, and mineralized nodule area of rat osteoblasts in each group were further detected.ResultsMEG3 and TXNIP were overexpressed while miR-214 was underexpressed in femoral tissues of OP rats. MEG3 silencing and miR-214 overexpression increased BMD, BV/TV, Tb.N, Tb.Th, the number of osteoblasts, collagen area and OPG expression, and downregulated PANKL of femoral tissues in OP rats. MEG3 silencing and miR-214 overexpression elevated Ca and P contents and reduced ALP content in OP rats’ blood, elevated viability, differentiation ability, COL-I and COL-Χ contents and ALP activity, and abated COL-II content of osteoblasts. MEG3 specifically bound to miR-214 to regulate TXNIP.ConclusionCollectively, we demonstrated that MEG3 silencing and miR-214 overexpression promote proliferation and differentiation of osteoblasts in OP by downregulating TXNIP, which further improves OP.

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Pulmonary reduction of an intravascular redox polymer

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.2001.280.6.l1290 ◽

2001 ◽

Vol 280 (6) ◽

pp. L1290-L1299 ◽

Cited By ~ 13

Author(s):

Said H. Audi ◽

Robert D. Bongard ◽

Yoshiyuki Okamoto ◽

Marilyn P. Merker ◽

David L. Roerig ◽

...

Keyword(s):

Endothelial Cells ◽

Superoxide Dismutase ◽

Electron Transport ◽

Kinetic Model ◽

Electron Acceptors ◽

Redox Polymer ◽

Pulmonary Endothelial Cells ◽

Equilibrium Level ◽

A Cell

Pulmonary endothelial cells in culture reduce external electron acceptors via transplasma membrane electron transport (TPMET). In studying endothelial TPMET in intact lungs, it is difficult to exclude intracellular reduction and reducing agents released by the lung. Therefore, we evaluated the role of endothelial TPMET in the reduction of a cell-impermeant redox polymer, toluidine blue O polyacrylamide (TBOP+), in intact rat lungs. When added to the perfusate recirculating through the lungs, the venous effluent TBOP+concentration decreased to an equilibrium level reflecting TBOP+ reduction and autooxidation of its reduced (TBOPH) form. Adding superoxide dismutase (SOD) to the perfusate increased the equilibrium TBOP+ concentration. Kinetic analysis indicated that the SOD effect could be attributed to elimination of the superoxide product of TBOPH autooxidation rather than of superoxide released by the lungs, and experiments with lung-conditioned perfusate excluded release of other TBOP+ reductants in sufficient quantities to cause significant TBOP+ reduction. Thus the results indicate that TBOP+ reduction is via TPMET and support the utility of TBOP+ and the kinetic model for investigating TPMET mechanisms and their adaptations to physiological and pathophysiological stresses in the intact lung.

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The role of non-coding RNA/microRNAs in cardiac disease

10.1093/med/9780198757269.003.0031 ◽

2018 ◽

Author(s):

Yolan J. Reckman ◽

Yigal M. Pinto

Keyword(s):

Myocardial Infarction ◽

Cardiac Hypertrophy ◽

Cardiac Disease ◽

Cardiac Development ◽

Rna Transcripts ◽

The Past ◽

Non Coding Rna ◽

Organ Systems ◽

Non Coding Rnas

In the past two decades, our knowledge about non-coding DNA has increased tremendously. While non-coding DNA was initially discarded as ‘junk DNA’, we are now aware of the important and often crucial roles of RNA transcripts that do not translate into protein. Non-coding RNAs (ncRNAs) play important functions in normal cellular homeostasis and also in many diseases across all organ systems. Among the different ncRNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been studied the most. In this chapter we discuss the role of miRNAs and lncRNAs in cardiac disease. We present examples of miRNAs with fundamental roles in cardiac development (miR-1), hypertrophy (myomiRs, miR-199, miR-1/133), fibrosis (miR-29, miR-21), myocardial infarction (miR-15, miR17~92), and arrhythmias/conduction (miR-1). We provide examples of lncRNAs related to cardiac hypertrophy (MHRT, CHRF), myocardial infarction (ANRIL, MIAT), and arrhythmias (KCNQ1OT1). We also discuss miRNAs and lncRNAs as potential therapeutic targets or biomarkers in cardiac disease.

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Long Non-Coding RNA and Acute Leukemia

International Journal of Molecular Sciences ◽

10.3390/ijms20030735 ◽

2019 ◽

Vol 20 (3) ◽

pp. 735 ◽

Cited By ~ 13

Author(s):

Gabriela Cruz-Miranda ◽

Alfredo Hidalgo-Miranda ◽

Diego Bárcenas-López ◽

Juan Núñez-Enríquez ◽

Julian Ramírez-Bello ◽

...

Keyword(s):

Acute Leukemia ◽

Hematological Malignancies ◽

Therapeutic Response ◽

Main Type ◽

Functional Classification ◽

Non Coding Rna ◽

Non Coding Rnas ◽

Long Non Coding Rna ◽

Cancer In Children

Acute leukemia (AL) is the main type of cancer in children worldwide. Mortality by this disease is high in developing countries and its etiology remains unanswered. Evidences showing the role of the long non-coding RNAs (lncRNAs) in the pathophysiology of hematological malignancies have increased drastically in the last decade. In addition to the contribution of these lncRNAs in leukemogenesis, recent studies have suggested that lncRNAs could be used as biomarkers in the diagnosis, prognosis, and therapeutic response in leukemia patients. The focus of this review is to describe the functional classification, biogenesis, and the role of lncRNAs in leukemogenesis, to summarize the evidence about the lncRNAs which are playing a role in AL, and how these genes could be useful as potential therapeutic targets.

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Interspecies Communication in Holobionts by Non-Coding RNA Exchange

International Journal of Molecular Sciences ◽

10.3390/ijms21072333 ◽

2020 ◽

Vol 21 (7) ◽

pp. 2333

Author(s):

Ana Lúcia Leitão ◽

Marina C. Costa ◽

André F. Gabriel ◽

Francisco J. Enguita

Keyword(s):

Target Cell ◽

Current Knowledge ◽

Cell Communication ◽

Special Focus ◽

Interspecies Communication ◽

Communication Signals ◽

Non Coding Rna ◽

Molecular Machinery ◽

Non Coding Rnas

Complex organisms are associations of different cells that coexist and collaborate creating a living consortium, the holobiont. The relationships between the holobiont members are essential for proper homeostasis of the organisms, and they are founded on the establishment of complex inter-connections between all the cells. Non-coding RNAs are regulatory molecules that can also act as communication signals between cells, being involved in either homeostasis or dysbiosis of the holobionts. Eukaryotic and prokaryotic cells can transmit signals via non-coding RNAs while using specific extracellular conveyors that travel to the target cell and can be translated into a regulatory response by dedicated molecular machinery. Within holobionts, non-coding RNA regulatory signaling is involved in symbiotic and pathogenic relationships among the cells. This review analyzes current knowledge regarding the role of non-coding RNAs in cell-to-cell communication, with a special focus on the signaling between cells in multi-organism consortia.

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