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

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.

scholarly journals Long Non-coding RNA GAS5 Worsens Coronary Atherosclerosis Through MicroRNA-194-3p/TXNIP Axis

2021 ◽  
Author(s):  
Yanbing Li ◽  
Yu Geng ◽  
Boda Zhou ◽  
Xuejiao Wu ◽  
Ou Zhang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Coronary Atherosclerosis ◽  
Growth Arrest ◽  
Interacting Protein ◽  
Expression Levels ◽  
Thioredoxin Interacting Protein ◽  
Non Coding Rna ◽  
Proliferation And Apoptosis ◽  
Regulatory Effects ◽  
Long Non Coding Rna

AbstractIt is formerly conducted that long non-coding RNA growth arrest-specific 5 (GAS5) is involved in the process of coronary atherosclerosis (AS). The regulatory effects of GAS5 on the microRNA (miR)-194-3p/thioredoxin-interacting protein (TXNIP) axis in AS have been insufficiently explored yet. Thereafter, this work is started from GAS5/miR-194-3p/TXNIP axis in AS. AS rats were modeled to obtain their coronary vascular tissues and endothelial cells (ECs), in which GAS5, miR-194-3p, and TXNIP expression were tested. ECs were identified by immunohistochemistry. The mechanism among GAS5, miR-194-3p, and TXNIP was determined. ECs were transfected with inhibited GAS5 or overexpressed miR-194-3p to decipher their functions in proliferation and apoptosis of ECs in AS. Raised GAS5 and TXNIP and degraded miR-194-3p expression levels exhibited in AS. GAS5 bound to miR-194-3p while miR-194-3p targeted TXNIP. Depleting GAS5 or restoring miR-194-3p enhanced proliferation and depressed apoptosis of ECs in AS. This work clearly manifests that inhibited GAS5 facilitates the growth of ECs through miR-194-3p-targeted TXNIP in AS, consolidating the basal reference to the curing for AS.

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

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.

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

2020 ◽  
Vol 40 (4) ◽  
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.

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

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.

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

Genes ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 459 ◽  
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.

scholarly journals Long Non-Coding RNA and Acute Leukemia

2019 ◽  
Vol 20 (3) ◽  
pp. 735 ◽  
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.

scholarly journals The Emerging Role of Long Non-Coding RNAs in Plant Defense Against Fungal Stress

2020 ◽  
Vol 21 (8) ◽  
pp. 2659
Author(s):  
Hong Zhang ◽  
Huan Guo ◽  
Weiguo Hu ◽  
Wanquan Ji
Keyword(s):  
Stress Responses ◽  
Higher Plants ◽  
Regulatory Elements ◽  
Cellular Functions ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Resistance To Infection ◽  
Regulatory Functions ◽  
Long Non Coding Rna

Growing interest and recent evidence have identified long non-coding RNA (lncRNA) as the potential regulatory elements for eukaryotes. LncRNAs can activate various transcriptional and post-transcriptional events that impact cellular functions though multiple regulatory functions. Recently, a large number of lncRNAs have also been identified in higher plants, and an understanding of their functional role in plant resistance to infection is just emerging. Here, we focus on their identification in crop plant, and discuss their potential regulatory functions and lncRNA-miRNA-mRNA network in plant pathogen stress responses, referring to possible examples in a model plant. The knowledge gained from a deeper understanding of this colossal special group of plant lncRNAs will help in the biotechnological improvement of crops.

scholarly journals Long Non-Coding RNA Associated with Cholesterol Homeostasis and Its Involvement in Metabolic Diseases

2020 ◽  
Vol 21 (21) ◽  
pp. 8337
Author(s):  
Kang-Hoon Lee ◽  
Hyeon-Ji Hwang ◽  
Je-Yoel Cho
Keyword(s):  
Metabolic Diseases ◽  
Disease Process ◽  
Cholesterol Homeostasis ◽  
Cell Component ◽  
Non Coding Rna ◽  
Systemic Level ◽  
Development Processes ◽  
Non Coding Rnas ◽  
Long Non Coding Rna

Cholesterol is an essential cell component that functions to create and maintain all kinds of cell membranes and lipoprotein particles. It is crucial to maintain the proper amount of cholesterol at both the cellular and systemic level. Recently, the importance of cholesterol has been reported not only in various cell development processes but also in the development of diseases. Furthermore, the involvement of long non-coding RNAs (lncRNAs), which are regarded as important epigenetic regulators in gene expression, has also been reported in cholesterol homeostasis. It is thus necessary to summarize the research on lncRNAs related to cholesterol with increased interest. This review organized the role of lncRNAs according to the major issues in cholesterol homeostasis: efflux, metabolism and synthesis, and disease process.

scholarly journals Long Non-coding RNA: Insight Into Mechanisms of Alzheimer's Disease

2022 ◽  
Vol 14 ◽  
Author(s):  
Zhen Lan ◽  
Yanting Chen ◽  
Jiali Jin ◽  
Yun Xu ◽  
Xiaolei Zhu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Vital Role ◽  
Biological Functions ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Long Non Coding Rna ◽  
Insight Into

Alzheimer's disease (AD), a heterogeneous neurodegenerative disorder, is the most common cause of dementia accounting for an estimated 60–80% of cases. The pathogenesis of AD remains unclear, and no curative treatment is available so far. Increasing evidence has revealed a vital role of non-coding RNAs (ncRNAs), especially long non-coding RNAs (lncRNAs), in AD. LncRNAs contribute to the pathogenesis of AD via modulating amyloid production, Tau hyperphosphorylation, mitochondrial dysfunction, oxidative stress, synaptic impairment and neuroinflammation. This review describes the biological functions and mechanisms of lncRNAs in AD, indicating that lncRNAs may provide potential therapeutic targets for the diagnosis and treatment of AD.

scholarly journals CIRCULAR RNA – miRNA MEDIATED INTERACTION IN MYOCARDIAL INFARCTION

2021 ◽  
Vol 27 (2) ◽  
pp. 3793-3798
Author(s):  
Yordanka Doneva ◽  
◽  
Veselin Valkov ◽  
Yavor Kashlov ◽  
Galya Mihaylova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Myocardial Infarction ◽  
Circular Rna ◽  
Biological Functions ◽  
Non Coding Rna ◽  
Circular Structure ◽  
Wide Range ◽  
Non Coding Rnas ◽  
Long Non Coding Rna

Circular RNA (circRNAs) belong to the long non-coding RNA family, but unlike the linear RNA in circular RNA, the 3’ and 5’ end in the RNA molecule are joined together, forming their circular structure. Until recently, circRNAs have been believed to be a side product of splicing, but now it is known that they have a wide range of biological functions, from regulators of gene expression to regulators of other non-coding RNAs - microRNAs (miRNAs). CircRNAs have the potential of being therapeutic targets and biomarkers for diseases. There are little data and only several investigations about this type of RNAs in myocardial infarction in humans. This review summarizes the role of some new circRNA – miRNA interactions in the development of Myocardial Infarction.

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