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The Neat Dance of COVID-19: NEAT1, DANCR, and Co-Modulated Cholinergic RNAs Link to Inflammation.

The COVID-19 pandemic exerts inflammation-related parasympathetic complications and post-infection manifestations with major inter-individua … x donors, we discovered sharp declines of the lung pathology-associated ncRNA DANCR and the nuclear paraspeckles forming neuroprotective ncRNA NEAT1. Accompanying increases in the acetylcholine-regulating transcripts capable of controlling inflammation co-appeared in SARS-CoV-2 infected but not H1N1 influenza infected lung cells. The lung cells-characteristic …

Mechanism of Cancer-Associated Fibroblasts-Derived NEAT1 Promoting Pancreatic Cancer Cell Stemness via the miR-101-3p/KDM3A Axis.

Pancreatic cancer (PC), a malignant neoplasm of the gastrointestinal tract, is linked to dismal prognoses and a restricted response to chemotherapy. Long noncoding RNAs (lncRNAs) play critical roles in regulating PC stemness. This study investigated the mechanism of cancer-associated fibroblasts (CAFs)-derived lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) promoting PC cell stemness via the microRNA-101-3p (miR-101-3p)/lysine demethylase 3A (KDM3A) axis. Human pancreatic CAFs were cultured in vitro and transfected with small interfering (si)-NEAT1. Extracellular vesicles (EVs) were i

Long Noncoding RNA NRAV Promotes Respiratory Syncytial Virus Replication by Targeting the MicroRNA miR-509-3p/Rab5c Axis To Regulate Vesicle Transportation.

Respiratory syncytial virus (RSV) is an enveloped RNA virus which is responsible for approximately 80% of lower respiratory tract infections in children. Current lines of evidence have supported the functional involvement of long noncoding RNA (lncRNA) in many viral infectious diseases. However, the overall biological effect and clinical role of lncRNAs in RSV infection remain unclear. In this study, lncRNAs related to respiratory virus infection were obtained from the lncRNA database, and we collected 144 clinical sputum specimens to identify lncRNAs related to RSV infection. Quantitative PCR

The Long Non-Coding RNAs in Neurodegenerative Diseases: Novel Mechanisms of Pathogenesis.

BACKGROUND: Long-non-coding RNAs (lncRNAs), RNA molecules longer than 200 nucleotides, have been involved in several biological processes an … al dementia and Amyotrophic lateral sclerosis the lncRNAs NEAT1_2 and MALAT1 co-localize at nuclear paraspeckles with TDP-43 and FUS proteins and their binding to TDP-43 is markedly increased in affected brains. In Parkinson's Disease the lncRNA UCHL1-AS1 acts by directly promoting translation of UCHL1 protein leading to perturbation of the ubiquitin-proteasom …

A novel ceRNA regulatory network involving the long noncoding NEAT1, miRNA-466f-3p and its mRNA target in osteoblast autophagy and osteoporosis.

Osteoporosis (OP) is a systemic metabolic disorder characterized by a reduction in bone tissue volume. LncRNAs have been reported to act as regulators of several human diseases. Specifically, lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) is involved in proliferation, differentiation and apoptosis in osteoclasts and bone marrow mesenchymal stem cells and regulates the occurrence and development of OP. However, the relationship between NEAT1 and osteoblast autophagy and its mechanism are still unclear. Western blotting of LC3 and P62 was used to evaluate the effect of fluid shear stre

Dynamics of the mammalian nucleus: can microscopic movements help us to understand our genes?

The cell is the basic building block of human life. Each of us has existed as a single cell--the fertilized egg--and each of us is made up o … r structures have been described, from the nucleolus (first described in 1835) to newly discovered 'paraspeckles' and 'clastosomes'. In fact, as increasing numbers of molecular probes become available, so the complexity of nuclear structure appears to expand. The functions of some of these structures are currently unknown. Those whose functions are, at least p …

NEAT1 lncRNA overexpression results in short-term progression and poor treatment outcome in childhood B-ALL.

Childhood acute lymphoblastic leukaemia (chALL) remains the most prevalent malignancy in children and adolescents. Improving risk stratification and providing personalized prognosis and treatment remain major clinical challenges. Herein, we analysed the clinical utility of NEAT1 lncRNA for the prognosis and prediction of treatment outcome of childhood B-cell precursor ALL (chB-ALL). NEAT1_1 isoform was quantified in bone marrow samples of chB-ALL patients at diagnosis (n = 160) and at the end of induction (n = 108) of ALL-BFM protocol, and in age-matched healthy children (n = 68). Relapse and

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… Alternative 3′‐end processing of long noncoding RNA initiates construction of nuclear paraspeckles. EMBO J. 2012;31(20):4020–4034. 29. Sunwoo H, Dinger ME, Wilusz JE, Amaral PP, Mattick JS, Spector DL. … Functional dissection of NEAT1 using genome editing reveals substantial localization of the NEAT1_1 isoform outside paraspeckles. RNA. 2017;23(6):872–881. 32. Nakagawa S, Naganuma T, Shioi G, Hirose T. Paraspeckles are subpopulation‐specific nuclear bodies that are not essential in mice. …

Biomolecular condensates as dynamic regulators of musculoskeletal homeostasis, disease, and therapeutic challenges.

Biomolecular condensates are membraneless assemblies that concentrate proteins, nucleic acids, and other biomolecules into dynamic cellular compartments. Liquid-liquid phase separation (LLPS) is one important route by which such condensates form, particularly when multivalent interactions generate liquid-like, reversible assemblies. However, not every condensate or disease-associated assembly should be explained solely by LLPS. In the musculoskeletal system, condensates have been linked to transcription, signal transduction, RNA metabolism, stress responses, tissue development, homeostasis, an

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… Table 1 Known membraneless organelles in musculoskeletal system diseases Membraneless organelle Key molecules Mechanism Function Reference Paraspeckles MATR3 and PABPN1 The PABPN1-MATR3 functional axis regulates paraspeckles through Neat1 Maintain the normal number of paraspeckles and mediate the nuclear … | MATR3 and PABPN1 | The PABPN1-MATR3 functional axis regulates paraspeckles through Neat1 | Maintain the normal number of paraspeckles and mediate the nuclear retention and editing of specific transcripts | 171 MEN ε/β and lncRNA | MEN ε/β lncRNA functions as a “scaffold” to assemble paraspeckles | …

LncRNA NEAT1 restrains the malignant biological characteristics of acute myeloid leukemia via regulating CTCF/CXCR2 axis.

Acute myeloid leukemia (AML) is notorious in the field of hematology for its poor efficacy, frustrating prognosis, and it is prone to refractory or relapsed conditions. Previous studies in our team have shown that some Long noncoding RNAs (lncRNAs) and chemokine receptors play key regulatory roles in AML. The findings of this study demonstrated that the expression of NEAT1 was atypically low in both clinical AML specimens and AML cell lines. Overexpression of NEAT1 was capable of attenuating the malignant biological characteristics of AML cells, including inhibiting the malignant proliferation

Non-Coding RNAs: The "Dark Side Matter" of the CLL Universe.

For many years in the field of onco-hematology much attention has been given to mutations in protein-coding genes or to genetic alterations, including large chromosomal losses or rearrangements. Despite this, biological and clinical needs in this sector remain unmet. Therefore, it is not surprising that recent studies have shifted from coded to non-coded matter. The discovery of non-coding RNAs (ncRNAs) has influenced several aspects related to the treatment of cancer. In particular, in chronic lymphocytic leukemia (CLL) the knowledge of ncRNAs and their contextualization have led to the ident

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… In particular, TP53 induces NEAT1, which is required for the assembly of subnuclear bodies known as paraspeckles [ 51 ]. … As a consequence, the formation of NEAT1-mediated paraspeckle prevents the accumulation of DNA damage and attenuates the activity of P53 in DNA-damaged cells, influencing cell fate decisions and response to therapy [ 51 ]. …

Long Non-Coding RNAs: Role in Testicular Cancers.

In the last few years lncRNAs have gained increasing attention among the scientific community, thanks to the discovery of their implication in many physio-pathological processes. In particular, their contribution to tumor initiation, progression, and response to treatment has attracted the interest of experts in the oncologic field for their potential clinical application. Testicular cancer is one of the tumors in which lncRNAs role is emerging. Said malignancies already have very effective treatments, which although lead to the development of quite serious treatment-related conditions, such a

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… An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles . Mol Cell ( 2009 ) 33 : 717–26 . 10.1016/j.molcel.2009.01.026 PMC2696186 19217333 42 Sasaki YT Ideue T Sano M Mituyama T Hirose T . … MEN epsilon/beta nuclear-retained non-coding RNAs are up-regulated upon muscle differentiation and are essential components of paraspeckles . Genome Res ( 2009 ) 19 : 347–59 . 10.1101/gr.087775.108 PMC2661813 19106332 44 Wang P Xu J Wang Y Cao X . …

Targeting Autophagy Using Long Non-Coding RNAs (LncRNAs): New Landscapes in the Arena of Cancer Therapeutics.

Cancer has become a global health hazard accounting for 10 million deaths in the year 2020. Although different treatment approaches have increased patient overall survival, treatment for advanced stages still suffers from poor clinical outcomes. The ever-increasing prevalence of cancer has led to a reanalysis of cellular and molecular events in the hope to identify and develop a cure for this multigenic disease. Autophagy, an evolutionary conserved catabolic process, eliminates protein aggregates and damaged organelles to maintain cellular homeostasis. Accumulating evidence has implicated the

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… In one study, sub-nuclear structures called “paraspeckles” were found to be present in the biogenesis of specific lncRNA [ 50 ]. … For instance, it was observed that nuclear paraspeckle assembly transcript 1 (NEAT1) lncRNA was highly expressed in CRC cells and tissues and promoted autophagy by directly targeting miR-34a levels. …

Extracellular RNA in melanoma: Advances, challenges, and opportunities.

Melanoma, a malignant mass lesion that originates in melanocytes and has a high rate of malignancy, metastasis, and mortality, is defined by these characteristics. Malignant melanoma is a kind of highly malignant tumor that produces melanin and has a high mortality rate. Its incidence accounts for 1%-3% of all malignant tumors and shows an obvious upward trend. The discovery of biomolecules for the diagnosis and treatment of malignant melanoma has important application value. So far, the exact molecular mechanism of melanoma development relevant signal pathway still remains unclear. According

WT1: The Hinge Between Anemia Correction and Cancer Development in Chronic Kidney Disease.

Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) emerge as promising agents to treat anemia in chronic kidney disease (CKD) but the major concern is their correlated risk of cancer development and progression. The Wilms' tumor gene, WT1, is transcriptionally regulated by HIF and is known to play a crucial role in tumorigenesis and invasiveness of certain types of cancers. From the mechanism of action of HIF-PHIs, to cancer hypoxia and the biological significance of WT1, this review will discuss the link between HIF, WT1, anemia correction, and cancer. We aimed to reveal the re

Modulating epigenetic modifications for cancer therapy (Review).

Cancer is a global public health concern. Alterations in epigenetic processes are among the earliest genomic aberrations occurring during cancer development and are closely related to progression. Unlike genetic mutations, aberrations in epigenetic processes are reversible, which opens the possibility for novel pharmacological treatments. Non‑coding RNAs (ncRNAs) represent an essential epigenetic mechanism, and emerging evidence links ncRNAs to carcinogenesis. Epigenetic drugs (epidrugs) are a group of promising target therapies for cancer treatment acting as coadjuvants to reverse drug resist

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… For instance, paraspeckles are mammalian-specific protein-rich nuclear organelles assembled on top of the lncRNA NEAT1. These organelles can trap RNAs and nucleoplasmic proteins, thereby reducing their availability ( 171 ). … gene repression in the p53 response Cell 142 409 419 2010 10.1016/j.cell.2010.06.040 20673990 PMC2956184 170 Dai X Kaushik AC Zhang J The emerging role of major regulatory RNAs in cancer control Front Oncol 9 920 2019 10.3389/fonc.2019.00920 31608229 PMC6771296 171 Fox AH Nakagawa S Hirose T Bond CS Paraspeckles …

Centromere protein E as a novel biomarker and potential therapeutic target for retinoblastoma.

Retinoblastoma is the most common intraocular malignancy during childhood. Currently, there is no effective treatment for metastatic retinoblastoma. We investigated potential biomarkers of retinoblastoma by utilizing three datasets from a public database. Functional enrichment analysis, including gene ontology, Kyoto encyclopedia of genes and genomes, gene set enrichment analysis and variation analysis, suggested that differentially expressed genes in retinoblastoma were enriched in accelerated cell cycle events. Protein-protein interaction analysis constructed a network consisting of six hub

Role of Long Non-Coding RNA X-Inactive-Specific Transcript (XIST) in Neuroinflammation and Myelination: Insights from Cerebral Organoids and Implications for Multiple Sclerosis.

Background/Objectives: X-inactive-specific transcript (XIST) is a factor that plays a role in neuroinflammation. This study investigated the role of XIST in neuronal development, neuroinflammation, myelination, and therapeutic responses within cerebral organoids in the context of Multiple Sclerosis (MS) pathogenesis. Methods: Human cerebral organoids with oligodendrocytes were produced from XIST-silenced H9 cells, and the mature organoids were subsequently treated with either FTY720 or DMF. Gene expression related to inflammation and myelination was subsequently analyzed via qRT-PCR. Immunoflu

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… In contrast, NEAT1 is absolutely required for the development of nuclear paraspeckles and plays a key role in modulating the expression of inflammatory genes during cellular stress. …

miRNAs and lncRNAs as Novel Therapeutic Targets to Improve Cancer Immunotherapy.

Immunotherapy is presently one of the most promising areas of investigation and development for the treatment of cancer. While immune checkpoint-blocking monoclonal antibodies and chimeric antigen receptor (CAR) T-cell-based therapy have recently provided in some cases valuable therapeutic options, the goal of cure has not yet been achieved for most malignancies and more efforts are urgently needed. Noncoding RNAs (ncRNA), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), regulate several biological processes via selective targeting of crucial molecular signaling pathways. Recent

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… Paraspeckles: Nuclear bodies built on long noncoding RNA J. Cell Biol. 2009 186 637 644 10.1083/jcb.200906113 19720872 PMC2742191 26. Guttman M. Amit I. Garber M. French C. Lin M.F. Feldser D. Huarte M. Zuk O. Carey B.W. Cassady J.P. …

Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies.

Hematologic malignancies are one of the most common cancers, and the incidence has been rising in recent decades. The clinical and molecular features of hematologic malignancies are highly heterogenous, and some hematologic malignancies are incurable, challenging the treatment, and prognosis of the patients. However, hematopoiesis and oncogenesis of hematologic malignancies are profoundly affected by epigenetic regulation. Studies have found that methylation-related mutations, abnormal methylation profiles of DNA, and abnormal histone deacetylase expression are recurrent in leukemia and lympho

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… proteins that regulate mRNA degradation. 554 – 556 Furthermore, some lncRNAs are complementarily base paired with miRNAs and thus can competitively bind with miRNAs or “sponging” miRNAs, and modulate corresponding miRNA-targeted gene expression. 471 , 557 Finally, lncRNAs are components of nuclear paraspeckle … , and paraspeckles act as scaffolds for regulatory molecules. 558 – 561 As described above, lncRNAs act extensively to regulate gene expression, and play important roles in development and various biological and disease contexts, including cancer. …

Euchromatic Histone Lysine Methyltransferase 2 Inhibition Enhances Carfilzomib Sensitivity and Overcomes Drug Resistance in Multiple Myeloma Cell Lines.

Proteasome inhibitors (PIs) are extensively used for the therapy of multiple myeloma. However, patients continuously relapse or are intrinsically resistant to this class of drugs. In addition, adverse toxic effects such as peripheral neuropathy and cardiotoxicity could arise. Here, to identify compounds that can increase the efficacy of PIs, we performed a functional screening using a library of small-molecule inhibitors covering key signaling pathways. Among the best synthetic lethal interactions, the euchromatic histone-lysine N-methyltransferase 2 (EHMT2) inhibitor UNC0642 displayed a coope

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… Expression levels of NONO, a nuclear protein primarily involved in paraspeckles function, are associated with several deregulated molecular pathways and poor clinical outcome in multiple myeloma. Discov. Oncol. 2022;13:124. doi: 10.1007/s12672-022-00582-2. 27. …