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Objective: Eugenol (EU) from cloves is highly effective against different tumors. The long noncoding ribonucleic acids (lncRNAs), which play a role of competing endogenous RNAs (ceRNAs), suppress microRNAs (miRNAs) involved in post-transcriptional regulatory networks. The present work focused on analyzing how EU affected pre-cancerous breast lesions (PBL). Methods: Initially, the gene expression profiles of patients (n = 880) in the National Center for Biotechnology Information (NCBI) database were analyzed. Further, we established a lncRNA-miRNA-mRNA ceRNA network through bioinformatics analysis and investigated mechanistic roles of lncRNAs as ceRNAs and the anti-tumor effect of EU using MCF-10AT cells in vitro as well as PBL model rats in vivo. Besides, Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), miR-383-5p, miR-9-5p, matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor-A (VEGF-A) expression was examined through quantitative reverse transcription polymerase chain reaction (RT-qPCR), Western blotting, and immunohistochemical staining analyses. Results: There were altogether 1162 mRNAs, 81 miRNAs, and 26 lncRNAs recognized as trend genes in breast cancer (BC) and pre-cancerous BC (pBC), constructing the ceRNA network using 3 lncRNAs, 3 miRNAs, and 38 mRNAs. It was observed that NEAT1, miR-383-5p, miR-9-5p, VEGF-A, and MMP-9 were downregulated in breast tumor cells in accordance with bioinformatics analysis. EU suppressed MCF-10AT cell growth, decreasing the NEAT1, VEGF-A, and MMP-9 levels and increasing miR-383-5p and miR-9-5p expressions in vitro and in vivo. Conclusion: In summary, the EU reduced the VEGF-A and MMP-9 expressions via NEAT1-mediated miR-383-5p and miR-9-5p against PBL, indicating that the EU may be a promising external drug to act against PBL.

In previous studies, we found radial extracorporeal shock wave (rESW), can promote the proliferation of neural stem cells (NSCs). Emerging evidence suggests that lncRNA NEAT1 can regulate NSCs proliferation. Whether lncRNA NEAT1 plays a role in the proliferation of NSC induced by shock waves is unclear. Cell Counting Kit-8（CCK 8) method was used to detect the proliferation of NSCs, and the relative protein and mRNA expression of related genes of Nestin, Cyclin D1 and P21 were detected by Western Blot and Quantitative real-time PCR (RT-qPCR) respectively. Immunofluorescence staining was used to observe the changes in the number of BrdU/nestin positive cells. Overexpression of NEAT1 and let 7 b in cells were used to explore whether rESW can rescue the decreased number of NSCs.We found that the optimal dose of R15 transmitter promoting NSCs proliferation is 1.5 bar, 500 pulse, 2 Hz. 1.2–1.5 bar showed a dose-dependent effect on the proliferation of NSCs, but it was negatively correlated with the proliferation effect of NSC when it was more than 1.5 bar. We revealed that let 7 b-P21 axis was involved in regulating the inhibition of NSC proliferation which was activated by NEAT1 in NSCs. In addition, we demonstrated that rESW treatment resulted in the decrease of NEAT1 expression, which was accompanied by the improved biological function including proliferation. Our results confirm that low-intensity rESW (1.5 bar，500 pulse，2 Hz) can promote the proliferation of NSCs through NEAT1-let 7 b-P21 axis.

The current outbreak of coronavirus disease 2019 (COVID-19) is a global emergency, as its rapid spread and high mortality rate, which poses a significant threat to public health. Innate immunity plays a crucial role in the primary defense against infections, and recent studies have highlighted the pivotal regulatory function of long non-coding RNAs (lncRNAs) in innate immune responses. This study aims to assess the circulating levels of lncRNAs namely ANRIL, THRIL, NEAT1, and MALAT1 in the blood of moderate and severe SARS-CoV-2 infected patients, in comparison to healthy individuals. Additionally, it aims to explore the potential of these lncRNAs as biomarkers for determining the severity of the disease. The blood samples were collected from a total of 38 moderate and 25 severe COVID-19 patients, along with 30 healthy controls. The total RNA was extracted and qPCR was performed to evaluate the blood levels of the lncRNAs. The results indicate significantly higher expression levels of lncRNAs ANRIL and THRIL in severe patients when compared to moderate patients (P value = 0.0307, P value = 0.0059, respectively). Moreover, the expression levels of lncRNAs ANRIL and THRIL were significantly up-regulated in both moderate and severe patients in comparison to the control group (P value

Skeletal muscle atrophy, manifested by a reduction in muscle size and quantity, is primarily attributed to excessive protein catabolism. FAM129B, an antioxidant protein, has been previously implicated in muscle growth and development in cattle. Aim of this study is to elucidate the role of FAM129B in muscle atrophy. FAM129B was consistently down-regulation in muscle atrophy models in vitro and in vivo and in human steroid-treated gluteus muscles. FAM129B depletion resulted in myotubes atrophy with reduced diameter, increased MuRF-1 and Atrogin-1. Conversely, FAM129B overexpression ameliorated muscle atrophy by increasing myotube diameter and reducing Atrogin-1 and MuRF-1. Mice overexpressing FAM129B exhibited resistance to muscle atrophy, evidenced by increased grip strength, increased tibial anterior weight, increased myofiber cross-sectional area and decreased MuRF-1 and Atrogin-1. RNA sequencing revealed NEAT1 as a downstream gene of FAM129B. Mechanistically, FAM129B was found to influence the stability of NEAT1 by directly binding to it. The enhanced stability of NEAT1 subsequently led to increased FoxO1 expression and subsequent protein degradation. Our study has provided evidence that the upregulation of FAM129B rescues the Dex-induced skeletal muscle atrophy, suggesting that FAM129B may be a potential target for alleviating skeletal muscle atrophy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)

Cancer-associated fibroblasts cells (CAFs) confer a rapid growth and metastasis ability of endometrial cancer (EC) via exosomes-mediated cellular communication. Long non-coding RNA nuclear enriched abundant transcript 1 (lncRNA NEAT1) drives the malignant phenotypes of EC cells. However, the role of exosomal NEAT1 from CAFs in EC progression remains ambiguous, which needs to be investigated. In our study, NEAT1 and YKL-40 were up-regulated, while miR-26a/b-5p was down-regulated in EC tissues. Moreover, NEAT1 expression was increased in CAF-exosomes compared with that in NF-exosomes. In addition, the exosomal NEAT1 derived from CAFs could transfer to EC cells and promote YKL-40 expression. Further exploration showed that exosomal NEAT1 enhanced YKL-40 expression via regulating miR-26a/b-5p-STAT3 axis in EC cells. More importantly, exosomal NEAT1 accelerated in vivo tumor growth via miR-26a/b-5p-STAT3-YKL-40 axis. Taken together, our study reveals that exosomal NEAT1 from CAFs contributes to EC progression via miR-26a/b-5p-mediated STAT3/YKL-40 pathway, which indicates the therapeutic potential of exosomal NEAT1 for treating EC.

Visualizing RNA dynamics is important for understanding RNA function. Catalytically dead (d) CRISPR-Cas13 systems have been established to image and track RNAs in living cells, but efficient dCas13 for RNA imaging is still limited. Here, we analyzed metagenomic and bacterial genomic databases to comprehensively screen Cas13 homologies for their RNA labeling capabilities in living mammalian cells. Among eight previously unreported dCas13 proteins that can be used for RNA labeling, dHgm4Cas13b and dMisCas13b displayed comparable, if not higher, efficiencies to the best-known ones when targeting endogenous MUC4 and NEAT1_2 by single guide (g) RNAs. Further examination of the labeling robustness of different dCas13 systems using the GCN4 repeats revealed that a minimum of 12 GCN4 repeats was required for dHgm4Cas13b and dMisCas13b imaging at the single RNA molecule level, while >24 GCN4 repeats were required for reported dLwaCas13a, dRfxCas13d and dPguCas13b. Importantly, by silencing pre-crRNA processing activity of dMisCas13b (ddMisCas13b) and further incorporating RNA aptamers including PP7, MS2, Pepper or BoxB to individual gRNAs, a CRISPRpalette system was developed to successfully achieve multi-color RNA visualization in living cells.

Acute lung injury (ALI), a common complication of sepsis, is characterized by the impairment and injury of pulmonary function. The nuclear factor kappa-B (NF-κB) pathway is activated in ALI. Tripartite motif-containing 37 (TRIM37) can activate the NF-κB pathway and is closely associated with inflammation. The purpose of our study is to reveal the role of TRIM37 in ALI. The present study revealed that TRIM37 presented high levels in lung tissues of ALI mice, and knockdown of TRIM37 alleviated lipopolysaccharide (LPS)-induced lung injury, inflammatory response, and cell apoptosis in vivo. In addition, knockdown of TRIM37 inhibited the inflammatory response, and cell apoptosis of LPS-treated WI-38 cells. Mechanistically, miR-944 was identified to bind with and negatively regulate TRIM37. Furthermore, NEAT1 was indicated to act as a competitive endogenous RNA to promote TRIM37 expression by sequestering miR-944. Detailly, NEAT1 bound with miR-944, negatively modulated miR-944 expression, and positively modulated TRIM37 expression. The rescue assays suggested that overexpression of TRIM37 rescued the influence of NEAT1 knockdown on cell apoptosis and inflammatory response. Overall, NEAT1 facilitated cell apoptosis and inflammatory response of WI-38 cells by the miR-944/TRIM37 axis in sepsis-induced ALI, implying that NEAT1 may provide a novel insight for the treatment of sepsis-induced ALI.

Long noncoding RNAs (lncRNAs), genomic “dark matter,” are deeply involved in diverse biological processes. The lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) is a highly participatory lncRNA; however, its roles in gastric cancer (GC) remain largely unexplored. Here, we demonstrated that the expression of NEAT1 was significantly increased and negatively correlated with prognosis in GC. Subsequent experiments confirmed that KLF5 can induce NEAT1 expression by binding to the NEAT1 promoter region. Further experiments revealed that NEAT1 silencing significantly suppressed cell proliferation both in vitro and in vivo and induced apoptosis. We used mRNA sequencing (mRNA-seq) to identify the preferentially affected genes linked to cell proliferation in cells with NEAT1 knockdown. Mechanistically, NEAT1 bound BRG1 (SMARCA4) directly, modulating H3K27me3 and H3K4me3 in the GADD45A promoter to regulate GADD45A-dependent G2/M cell cycle progression. In addition, BRG1 was significantly upregulated and correlated with outcomes in GC; moreover, it promoted cell proliferation both in vitro and in vivo. Taken together, our data support the importance of NEAT1 in promoting GC tumorigenesis and indicate that NEAT1 might be a diagnostic and therapeutic target in GC.

Hypoxic-ischemic brain damage (HIBD) is a major cause of fatality and morbidity in neonates. However, current treatment approaches to alleviate HIBD are not effective. Various studies have highlighted the role of microRNAs (miRNAs) in various biological functions in multiple diseases. This study investigated the role of miR-339-5p in HIBD progression. Neonatal HIBD mouse model was induced by ligation of the right common carotid artery. Neuronal cell model exposed to oxygen-glucose deprivation (OGD) was also established. The miR-339-5p expression in mouse brain tissues and neuronal cells was quantified, and the effects of miR-339-5p on neuronal cell activity and apoptosis induced by hypoxia-ischemia were explored. The overexpression or knockdown of long non-coding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) in hippocampal neurons was used to determine the effect of lncRNA NEAT1 on the expression of miR-339-5p and homeobox A1 (HOXA1) and apoptosis. Short hairpin RNA targeting lncRNA NEAT1 and miR-339-5p antagomir were used in neonatal HIBD mice to identify their roles in HIBD. Our results revealed that miR-339-5p was downregulated in neonatal HIBD mice and neuronal cells exposed to OGD. Downregulated miR-339-5p promoted neuronal cell viability and suppressed apoptosis during hypoxia-ischemia. Moreover, lncRNA NEAT1 competitively bound to miR-339-5p to increase HOXA1 expression and inhibited neuronal cell apoptosis under hypoxic-ischemic conditions. The key observations of the current study present evidence demonstrating that lncRNA NEAT1 upregulated HOXA1 to alleviate HIBD in mice by binding to miR-339-5p.

Altered expression of long noncoding RNA (lncRNA), longer than 200 nucleotides without potential for coding protein, has been observed in diverse human diseases including viral diseases. It is largely unknown whether lncRNA would deregulate in SARS-CoV-2 infection, causing ongoing pandemic COVID-19. To identify, if lncRNA was deregulated in SARS-CoV-2 infected cells, we analyzed in silico the data in GSE147507. It was revealed that expression of 20 lncRNA like MALAT1, NEAT1 was increased and 4 lncRNA like PART1, TP53TG1 was decreased in at least two independent cell lines infected with SARS-CoV-2. Expression of NEAT1 was also increased in lungs tissue of COVID-19 patients. The deregulated lncRNA could interact with more than 2800 genes/proteins and 422 microRNAs as revealed from the database that catalogs experimentally determined interactions. Analysis with the interacting gene/protein partners of deregulated lncRNAs revealed that these genes/proteins were associated with many pathways related to viral infection, inflammation and immune functions. To find out whether these lncRNAs could be regulated by STATs and interferon regulatory factors (IRFs), we used ChIPBase v2.0 that catalogs experimentally determined binding from ChIP-seq data. It was revealed that any one of the transcription factors IRF1, IRF4, STAT1, STAT3 and STAT5A had experimentally determined binding at regions within -5kb to +1kb of the deregulated lncRNAs in at least 2 independent cell lines/conditions. Our analysis revealed that several lncRNAs could be regulated by IRF1, IRF4 STAT1 and STAT3 in response to SARS-CoV-2 infection and lncRNAs might be involved in antiviral response. However, these in silico observations are necessary to be validated experimentally.

Glioblastoma (GBM) is the most prevalent and deadly primary brain tumor type, with a discouragingly low survival rate and few effective treatments. An important function of the EGFR signalling pathway in the development of GBM is to affect tumor proliferation, persistence, and treatment resistance. Advances in molecular biology in the last several years have shown how important ncRNAs are for controlling a wide range of biological activities, including cancer progression and development. NcRNAs have become important post-transcriptional regulators of gene expression, and they may affect the EGFR pathway by either directly targeting EGFR or by modifying important transcription factors and downstream signalling molecules. The EGFR pathway is aberrantly activated in response to the dysregulation of certain ncRNAs, which has been linked to GBM carcinogenesis, treatment resistance, and unfavourable patient outcomes. We review the literature on miRNAs, circRNAs and lncRNAs that are implicated in the regulation of EGFR signalling in GBM, discussing their mechanisms of action, interactions with the signalling pathway, and implications for GBM therapy. Furthermore, we explore the potential of ncRNA-based strategies to overcome resistance to EGFR-targeted therapies, including the use of ncRNA mimics or inhibitors to modulate the activity of key regulators within the pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: Cognitive impairment poses a considerable health challenge in the context of type 2 diabetes mellitus (T2DM), emphasizing the need for effective interventions. This study delves into the therapeutic efficacy of quercetin, a natural flavonoid, in mitigating cognitive impairment induced by T2DM in murine models., Materials and Methods: Serum exosome samples were obtained from both T2DM-related and healthy mice for transcriptome sequencing, enabling the identification of differentially expressed mRNAs and long noncoding RNAs (lncRNAs). Subsequent experiments were conducted to ascertain the binding affinity between mmu-miR-129-5p, NEAT1 and BDNF. The structural characteristics and dimensions of isolated exosomes were scrutinized, and the expression levels of exosome-associated proteins were quantified. Primary mouse hippocampal neurons were cultured for in vitro validation, assessing the expression of pertinent genes as well as neuronal vitality, proliferation, and apoptosis capabilities. For in vivo validation, a T2DM mouse model was established, and quercetin treatment was administered. Changes in various parameters, cognitive ability, and the expression of insulin-related proteins, along with pivotal signaling pathways, were monitored., Key Findings: Analysis of serum exosomes from T2DM mice revealed dysregulation of NEAT1, mmu-miR-129-5p, and BDNF. In vitro investigations demonstrated that NEAT1 upregulated BDNF expression by inhibiting mmu-miR-129-5p. Overexpression of mmu-miR-129-5p or silencing NEAT1 resulted in the downregulation of insulin-related protein expression, enhanced apoptosis, and suppressed neuronal proliferation. In vivo studies validated that quercetin treatment significantly ameliorated T2DM-related cognitive impairment in mice., Significance: These findings suggest that quercetin holds promise in inhibiting hippocampal neuron apoptosis and improving T2DM-related cognitive impairment by modulating the NEAT1/miR-129-5p/BDNF pathway within serum exosomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Nono is a component of the para-speckle, which stores and processes RNA. Mouse embryonic stem cells (mESCs) lack para-speckles, leaving the function of Nono in mESCs unclear. Here, we find that Nono functions as a chromatin regulator cooperating with Erk to regulate mESC pluripotency. We report that Nono loss results in robust self-renewing mESCs with epigenomic and transcriptomic features resembling the 2i (GSK and Erk inhibitors)-induced “ground state.” Erk interacts with and is required for Nono localization to a subset of bivalent genes that have high levels of poised RNA polymerase. Nono loss compromises Erk activation and RNA polymerase poising at its target bivalent genes in undifferentiated mESCs, thus disrupting target gene activation and differentiation. These findings argue that Nono collaborates with Erk signaling to regulate the integrity of bivalent domains and mESC pluripotency.

The long noncoding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) has been shown to be involved in the pathogenesis of several diseases. Herein, we discuss recent developments and insights into NEAT1 and its contribution to a variety of immune disorders. Our evaluations revealed that NEAT1's function in immune diseases seems to be focused on the modulation of paraspeckle expression and it is primarily associated with the nuclear retention of its mRNA. NEAT1 is also involved in the sequestration of paraspeckle proteins and in affecting the transcriptional expression of specific immune regulators. The expression of NEAT1 may be aberrantly upregulated in several immune pathologies, indicating that it could serve as a potential prognostic biomarker in these conditions. We summarized describing the expression changes and the role of NEAT1 in several immune diseases. We also described the mechanism of its regulation of the immune cell differentiation and function of NEAT1 in different disease., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Breast cancer (BC) is the most common cancer in women. Despite the effectiveness of conventional therapies, they cause detrimental side effects. Glycosyl-Phosphatidyl-Inositol (GPI) pathway is a conserved pathway that culminates in the generation of GPI anchored proteins (GPI-AP). Phosphatidyl-Inositol-Glycan Biosynthesis Class C (PIG-C) is the first step in GPI pathway and upon its overexpression, Mesothelin (MSLN); an oncogenic GPI-AP, expression is induced. Therefore, blocking GPI pathway is a potential therapy through which multiple pathways can be rectified. Recombinant GPI-CD80 proved to be a potent immunostimulatory protein and currently being evaluated as tumor vaccine. In fact, CD80 is a unique immunomodulator that binds to CD28, CTLA-4 and PD-L1. Furthermore, research advancement showed that non-coding RNAs (ncRNAs) are key epigenetic modulators. Therefore, epigenetic tuning of GPI-APs remains an unexplored area. This study aims at investigating the potential role of ncRNAs in regulating MSLN, PIG-C and CD80 in BC., Methods: Potential ncRNAs were filtered by bioinformatics algorithms. MDA-MB-231 cells were transfected with RNA oligonucleotides. Surface CD80 and MSLN were assessed by FACS and immunofluorescence. Gene expression was tested by q-PCR., Results: PIG-C gene was overexpressed in TNBC and its manipulation altered MSLN surface level. Aligning with bioinformatics analysis, miR-2355 manipulated PIG-C and MSLN expression, while miR-455 manipulated CD80 expression. NEAT1 sponged both miRNAs. Paradoxically, NEAT1 lowered PIG-C gene expression while increased MSLN gene expression., Conclusion: This study unravels novel immunotherapeutic targets for TNBC. NEAT1 is potential immunomodulator by sponging several miRNAs. Finally, this study highlights GPI pathway applications, therefore integrating epigenetics, post-translational modifications and immunomodulation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Parkinson disease is a neurodegenerative disease and is characterized by resting tremor, dementia, and gait disorder. Previous studies have indicated that long noncoding RNA participates in the regulation of the pathogenesis of Parkinson disease. The study aimed to reveal the effects of long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) on 1-methyl-4-phenylpyridine (MPP + )-induced human neuroblastoma cell injury and the underlying mechanism., Methods: The expressions of NEAT1, microRNA (miR)-519a-3p, and transcription factor specific protein 1 (SP1) were detected by quantitative real-time polymerase chain reaction. The protein expressions of SP1 and inflammation-related factors were determined by Western blot. Cell viability was determined by 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptosis was investigated by flow cytometry analysis. The targeting relationship between miR-519a-3p and NEAT1 or SP1 was predicted by starBase online database and verified by a dual-luciferase reporter assay., Results: NEAT1 and SP1 expressions were significantly upregulated, whereas miR-519a-3p was downregulated in MPP + -treated neuroblastoma cells in a dose- and time-dependent manner when compared with control groups. NEAT1 knockdown restrained MPP + -induced repression of cell viability and promotion of cell apoptosis and inflammation. Additionally, NEAT1 served as a sponge of miR-519a-3p and regulated MPP + -caused cell injury by interacting with miR-519a-3p. Also, SP1, a target gene of miR-519a-3p, rescued miR-519a-3p-mediated actions under MPP + treatment. Importantly, NEAT1 stimulated SP1 expression through interaction with miR-519a-3p., Conclusions: NEAT1 silencing protected against MPP + -induced neuroblastoma cell injury by regulating the miR-519a-3p/SP1 pathway. This finding provides a novel direction for the development of therapeutic strategies for Parkinson disease., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Rosacea is a complex, chronic, and recurrent dermatologic condition that adversely affects quality of life and self-esteem. However, clinical relevance and molecular mechanisms underlying NEAT1 influence in rosacea remain unclear., Objective: The present study aims to investigate the dynamics and influences of lncRNAs, miRNAs, and mRNAs in rosacea patients, and to explore the impacts of NEAT1 treatments on miR-196a-5p and S100A9 expression in LL37-treated HaCaT cells., Methods: RNA-sequencing of skin tissues from rosacea patients and integrative analyses facilitated comprehensive exploration of lncRNA, mRNA, and miRNA networks. We identified differentially expressed lncRNAs in paired rosacea afflicted and non-lesioned tissues by hub lncRNAs in the ceRNA network. The role of NEAT1 in LL37-treated HaCaT cells was identified by in vitro experiments., Results: There were 237 lncRNAs, 38 miRNAs, and 1784 mRNAs in lesioned skin compared to non-lesioned skin in six rosacea patients. NEAT1 was upregulated in rosacea skin and in LL37-treated HaCaT cells. Moreover, inflammatory damage was able to be reduced in vitro after knockdown of NEAT1. Finally, NEAT1 was able to directly interact with miR-196a-5p, and downregulating miR-196a-5p was efficient in reversing the influence of NEAT1 siRNA on S100A9., Conclusion: We have completed the first genome-wide lncRNA profiling of paired lesioned and non-lesioned samples from rosacea afflicted patients. The NEAT1/miR-196a-5p/S100A9 axis may have played an important role in the dynamics underlying inflammatory responses of rosacea. NEAT1 may have functioned as a competing endogenous RNA which regulated inflammatory responses in rosacea by sponging miR-196a-5p and upregulating S100A9 expression., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2021 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Background: Nonalcoholic fatty liver disease (NAFLD) is a severe liver disease, which influences the health of people worldwide. However, the specific mechanism of the disease remains unknown, and effective treatments are still lacking. It was reported that Nuclear enriched abundant transcript 1 (NEAT1) obviously was up-regulated in NAFLD model. But the role and underlying mechanism of NEAT1 in NAFLD is unclear., Methods: HepG2 cells were treated by free fatty acids (FFA) and C57BL/6J mice were treated by high-fat diet to establish NAFLD in vitro and in vivo models, respectively. Cell transfection was applied to regulate the expression of NEAT1, ROCK1, and miR-146a-5p. Western blotting and qRT-PCR were used for measuring expression of protein and mRNA level, respectively. Dual luciferase assay was used to detect the target relationship. Oil Red O staining was used to measure the lipid accumulation. HE staining was used for observing pathological feature of liver tissues., Results: High levels of NEAT1 and ROCK1, and low level of miR-146a-5p were identified in NAFLD models. NEAT1 could target miR-146a-5p to promote ROCK1 expression. Knockdown of NEAT1, overexpression of miR-146a-5p and knockdown of ROCK1 inhibited lipid accumulation through activating AMPK pathway., Conclusion: NEAT1 may regulate NAFLD through miR-146a-5p targeting ROCK1, and further affect AMPK/SREBP pathway. This study may provide a new thought for the treatment of NAFLD., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Huntington Disease (HD) is a neurodegenerative disorder caused by expanded CAG repeats in the exon1 of huntingtin gene (HTT). The mutant HTT affects the transcriptional profile of neurons by disrupting the activities of transcriptional machinery and alters expression of many genes. In this study, we identified dysregulated non-coding RNAs (ncRNAs) in medium spiny neurons of 4-week-old HD model mouse. Also, we observed the intracellular localizations of Abhd11os and Neat1 ncRNAs by ViewRNA in situ hybridization, which could provide more precise detection, suggesting that it is a useful method to investigate the expression changes of genes with low expression levels., (Copyright © 2018 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.)

Background: Nonalcoholic fatty liver disease (NAFLD) is a severe liver disease, which influences the health of people worldwide. However, the mechanism modulating the pathogenesis of NAFLD remains elusive. It was reported that nuclear enriched abundant transcript 1 (NEAT1) and microRNA-140 (miR-140) could regulate lipogenesis, but whether they could influence NAFLD are still unknown., Methods: HepG2 cells were treated by free fatty acids (FFA) to establish the model of NAFLD in vitro, and C57 mice were treated by high-fat diet to establish the model of NAFLD in vivo. Cell transfection was applied to regulate the expression of NEAT1 and miR-140. Western blotting and qRT-PCR were applied for measuring expression of protein and mRNA, respectively. HE staining and Oil Red O staining were used for observing liver tissues., Results: NEAT1 and miR-140 are upregulated in hepacytes under the NAFLD conditions. NEAT1 directly binds to miR-140 and acts synergistically with miR-140 to exacerbate the progression of NAFLD. Reciprocally, silence of miR-140 or NEAT1 alleviates the severity of NAFLD. The mechanistical study shows that the axis of NEAT1-miR-140 inactivates AMPK/SREBP-1 signaling during the NAFLD. ., Conclusion: The NEAT1-miR-140 axis play a crucial role in modulation of NAFLD via inactivation of AMPK/SREBP1 signaling. This study may provide a novel insight for the treatment of NAFLD., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The relevance of RNA processing has been increasingly recognized in a variety of diseases. We previously identified serine/arginine-rich splicing factor 1 (SRSF1) as an oncodriver in glioma via splicing control. However, its splicing-independent roles and mechanisms are poorly defined in glioma. In this study, by integrating the data mining of SRSF1-co-expressed genes, SRSF1-affected genes and experimental studies, we demonstrated that SRSF1 was the most highly expressed SRSF in the 9 tumor types tested, and it was a crucial cell cycle regulator in glioma. Importantly, we identified nuclear paraspeckle assembly transcript1 (NEAT1), an upregulated long non-coding RNA (lncRNA) in glioma, as a target of SRSF1. Endogenous NEAT1 inhibition resembled the effect of SRSF1 knockdown on glioma cell proliferation by retarding cell cycle. Mechanistically, we proved that SRSF1 bound to NEAT1 and facilitated its RNA stability. The positive correlation between SRSF1 and NEAT1 levels in cancers further supported the positive regulation of NEAT1 by SRSF1. Collectively, our results provide novel insights on the splicing-independent mechanisms of SRSF1 in glioma, and confirm that NEAT1, whose stability maintained by SRSF1, implicates gliomagenesis by regulating cell cycle. Both SRSF1 and NEAT1 may serve as promising targets for antineoplastic therapies., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Immunotherapy is a promising method for the treatment of hepatocellular carcinoma (HCC), in which CD8 + T cells play a key role. The influence of long noncoding RNA (lncRNA) nuclear-enriched autosomal transcript 1(NEAT1) on the antitumor activity of CD8 + T cells was clarified in this study., Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from HCC patients, and the expressions of NEAT1 and Tim-3 were determined by qRT-PCR and western blot, respectively. CD8 + T cell apoptosis and cell percentage were analyzed via flow cytometry. The cytolysis activity of CD8 + T cells against HCC cells was examined. RNA immunoprecipitation (RIP) and RNA pull-down assay were performed to explore the interaction between NEAT1 and miR-155., Results: NEAT1 and Tim-3 were up-regulated in the PBMCs of patients with HCC (n = 20) compared with healthy subjects (n = 20). Down-regulation of NEAT1 restrained CD8 + T cell apoptosis and enhanced the cytolysis activity, while interference of miR-155 showed the opposite effects by up-regulating Tim-3. Binding and interaction between NEAT1 and miR-155 were validated in CD8 + T cells. Down-regulation of NEAT1 restrained CD8 + T cell apoptosis and enhanced the cytolysis activity through the miR-155/Tim-3 pathway. Repression of NEAT1 suppressed tumor growth in HCC mice., Conclusion: Via modulating the miR-155/Tim-3 pathway, repression of NEAT1 restrained CD8 + T cell apoptosis and enhanced the cytolysis activity against HCC, implying an effective target for improving the outcome of immunotherapy., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Long non-coding RNAs (lncRNAs) have been identified to exert crucial roles in tumorigenesis and can serve as novel biomarkers for cancer therapy including lung cancer. Cisplatin is a first-line chemotherapeutic agent in non-small cell lung cancer (NSCLC), but the therapeutic effect is unsatisfactory, partly due to drug resistance. Emerging evidence showed that chemo-resistance is associated with acquisition of cancer stem cell (CSC)-like properties. Cisplatin resistance remains a major obstacle in the treatment of lung cancer, and its mechanism is still not fully elucidated. Meanwhile, CSCs have been involved in tumor metastasis, tumor recurrence and chemotherapy resistance. So far, the mechanism of nuclear enriched abundant transcript 1 (NEAT1) in modulating CSCs in lung cancer remains barely known. Therefore, we aimed to explore the correlation between NEAT1 and cancer stem cells in lung cancer. In our current study, we observed that CSC-like traits were much more enriched in cisplatin-resistant A549/CDDP cells. In addition, NEAT1 was obviously up-regulated in A549/CDDP cells compared with parental A549 cells. Knockdown of NEAT1 decreased the CSC-like properties of A549/CDDP cells through inhibiting tumor cell sphere volume, repressing CSC-like biomarkers levels and restraining CD44 positive cell ratios. Oppositely, overexpression of NEAT1 enhanced the stemness respectively. Moreover, it has been reported that Wnt pathway is implicated in many vital cellular functions including cancer stem cells. Here, it was exhibited that Wnt signal pathway was inactivated by knockdown of NEAT1 whereas activated by NEAT1 overexpression in A549/CDDP cells. Taken these together, it was indicated that NEAT1 could exert a novel biological role in NSCLC chemo-resistance., (Copyright © 2018. Published by Elsevier B.V.)

Background and Aims: This study aimed to investigate the effects of long non-coding RNA (lncRNA)-nuclear-enriched abundant transcript (Neat1) on myocardial ischemia reperfusion injury in diabetic rats ex vivo and in vivo., Methods: Screening for LncRNA Neat1 expression was performed in rat myocardial tissues using microarray analysis and verified by qRT-PCR. Cell viability of rat cardiomyocytes was analyzed by MTT assay. Levels of autophagy-related proteins Atg7, Atg5, LC3-II/LC3-I and p62 were determined by Western blot assay. Left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular ejection fraction (LVEF) and fractioning shortening were obtained by transthoracic echocardiography. Left ventricular end systolic pressure (LVESP), left ventricular end diastolic pressure (LVEDP), maximum rate of increase or decrease of left ventricular pressure (±dp/dtmax) and heart rate were obtained by computer algorithms and an interactive videographics programme. Myocardial infarct size was determined by Evans blue and triphenyltetrazolium chloride (TTC) staining. Myocardial apoptotic index was analyzed by TUNEL assay and immunohistochemical staining. Autophagic flux was examined by evaluating fluorescent LC3 puncta., Results: Neat1 was highly expressed in ischemia reperfusion-treated diabetic rat myocardial tissues. Overexpression of Neat1 promoted the production of lactate dehydrogenase, inhibited superoxide dismutase content and cardiomyocyte viability. Neat1 overexpression also promoted the production of serum myocardial enzymes, including creatine kinase and creatine kinase-MB, and increased infarct size. By promoting myocardial apoptosis and autophagy, Neat1 aggravated myocardial ischemia reperfusion (I/R) injury in diabetic rats. Neat1 promoted cardiomyocyte autophagy by up-regulating Foxo1 expression to increase hypoxia-reoxygenation injury., Conclusions: I/R treatment caused more injuries in diabetic rats compared with normal rats. Elevated Neat1 expression aggravates myocardial ischemia reperfusion injury via activation of apoptosis and autophagy in diabetic rats. Foxo1 is one of the molecular mechanisms underlying Neat1-induced autophagy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Long noncoding RNAs (lncRNAs) are fundamental genomic regulatory factors under various physiological and pathological conditions. A class of lncRNAs termed architectural RNAs (arcRNAs) plays an essential scaffolding role in building nuclear bodies. NEAT1 arcRNA is an abundant, nuclear-retained lncRNA that constructs paraspeckle nuclear bodies. NEAT1 is upregulated in various developmental and disease conditions including cancer and virus infection. However, it remains unclear how elevated expression of NEAT1 influences such conditions. Here, we set up an experimental method to selectively increase NEAT1 expression. We applied the synergistic activation mediator (SAM) system using catalytically dead Cas9 (dCas9) proteins to activate transcription of the NEAT1 gene. We examined 10 pre-designed and 15 originally designed single-guide RNAs (sgRNAs) in the NEAT1 promoter region for CRISPR activation (CRISPRa). We validated several sgRNAs that we designed for the SAM system to strongly activate NEAT1 expression in two human cell lines and induced formation of paraspeckles with intact core-shell structures. Thus, this selective NEAT1 upregulation method using the SAM system would be useful for further functional analyses of NEAT1 lncRNA in both basic and applied research., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Emerging evidences have shown that long non-coding RNAs (lncRNAs) play critical roles in cancer development and cancer therapy. LncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) is indispensable during acute promyelocytic leukemia (APL) cell differentiation induced by all-trans retinoic acid (ATRA). However, the precise mechanism of NEAT1 upregulation has not been fully understood. In this study, we performed chromatin immunoprecipitation and luciferase reporter assays to demonstrate that C/EBP family transcription factor C/EBPβ bind to and transactivate the promoter of lncRNA NEAT1 through the C/EBPβ binding sites both around -54 bp and -1453 bp upstream of the transcription start site. Moreover, the expression of C/EBPβ was increased after ATRA treatment, and the binding of C/EBPβ in the NEAT1 promoter was also dramatically increased. Finally, knockdown of C/EBPβ significantly reduced the ATRA-induced upregulation of NEAT1. In conclusion, C/EBPβ directly activates the expression of NEAT1 through binding to the promoter of NEAT1. Knockdown of C/EBPβ impairs ATRA-induced transcriptional activation of NEAT1. Our data indicate that C/EBPβ contributes to ATRA-induced activation of NEAT1 during APL cell differentiation. Our results enrich our knowledge on the regulation of lncRNAs and the regulatory role of C/EBPβ in APL cell differentiation., (Copyright © 2017. Published by Elsevier Inc.)

Background: Long non-coding RNA nuclear paraspeckle assembly transcript 1 (lncRNA NEAT1) was found to be closely related to the pathological changes in brain and nervous system. However, the role of NEAT1 and its potential mechanism in Parkinson's disease (PD) largely remain uncharacterized., Methods: In this study, PD mouse model was established by intraperitoneal injection of MPTP. The numbers of TH + neurons, NEAT1 expression and the level of PINK1, LC3-II, LC3-I protein were assessed in PD mice. SH-SY5Y cells were treated with MPP + as PD cell model. RNA pull-down assay was used to identify the interaction between NEAT1 and PINK1 in vitro. The endogenous expression of NEAT1 was modified by lentiviral vector carrying interference sequence for NEAT1 in vivo., Results: The numbers of TH + neurons significantly decreased in PD mice compared with the control. The expressions of NEAT1, PINK1 protein and LC3-II/LC3-I level were increased by MPTP in vitro and in vivo. Moreover, NEAT1 positively regulated the protein level of PINK1 through inhibition of PINK1 protein degradation. And NEAT1 mediated the effects of MPP + on SH-SY5Y cells through stabilization of PINK1 protein. The results of in vivo experiments revealed that NEAT1 knockdown could effectively suppress MPTP-induced autophagy in vivo that alleviated dopaminergic neuronal injury., Conclusion: LncRNA NEAT1 promoted the MPTP-induced autophagy in PD through stabilization of PINK1 protein., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Steroid receptor co-activator3 (SRC3) has been known to severe as an androgen receptor (AR) coactivator and is involved in the prostate cancer progression. Non-coding RNA (ncRNA) plays an important role in the cancer progression. However, the mechanism underlying the relationship between ncRNA and AR coactivators is still unclear. Here, we found a ncRNA, Nuclear Enriched Abundant Transcript 1 (NEAT1), was able to interact with SRC3 in the prostate cancer cell lines. NEAT1 can upregulate the AKT phosphorylation via a SRC3/IGF1R pathway. In function, NEAT1 promoted the prostate cancer cell growth through IGF1R/AKT signaling pathway. The NEAT1, SRC3, and IGF1R were highly expressed in the patients' samples of prostate cancer. Therefore, we found a novel SRC3 binding ncRNA that can promote the prostate cancer cell growth through SRC3/IGF1R/AKT pathway., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Long non-coding RNAs play a significant role in cancer metastasis. Studies have demonstrated that LncRNA NEAT1 promotes cancer progression. We aimed to explore whether NEAT1 regulated growth and invasion in breast cancer cells. We provided evidence that lncRNA NEAT1 was up-regulated in breast cancer cell lines and tissues. NEAT1 promoted invasion through inducing Epithelial-mesenchymal transition (EMT) and NEAT1 played a role in 5-fluorouracil (5-FU) resistance. In addition, we revealed a reciprocal repression between NEAT1 and miR-211. Furthermore, the EMT-inducer HMGA2 was identified as a down-stream target of miR-211. LncRNA NEAT1 induced EMT and 5-FU resistance through the miR-211/HMGA2 axis. Our findings suggest that lncRNA NEAT1 could be a new diagnostic biomarker and therapy target for breast cancer., (Copyright © 2017. Published by Elsevier B.V.)

Objective: Bexarotene treatments exert neuroprotective effects on mice following traumatic brain injury (TBI). The present study aims to investigate the potential roles of the long noncoding RNA Neat1 in the neuroprotective effects of bexarotene., Materials and Methods: Adult male C57BL/6J mice (n=80) and newborn mice (within 24h after birth) (n=20) were used to generate a "controlled cortical impact" (CCI) model and harvest primary cortex neurons, respectively. The HT22 cell line and the BV2 cell line were cultured under "normal" or "oxygen/glucose-deprived" (OGD) conditions. The relationship between RXR-α and the Neat1 promoter was clarified using ChIP-qPCR and dual-luciferase reporter gene assays. The mRNA alterations induced by Neat1 knockdown were measured using next-generation RNA sequencing. Proteins were captured by Neat1, pulled down and subjected to mass spectrometry. The neurological severity score, rotarod test and water maze test were employed to measure the animals' motor and cognitive functions., Results: Bexarotene prominently up-regulated the Neat1 level in an RXR-α-dependent manner. Neat1 knockdown induced significant changes in mRNA expression, and the altered mRNAs were involved in many biological processes, including synapse formation and axon guidance. In primary neurons, Neat1 knockdown inhibited and Neat1 over-expression prompted axon elongation. Multiple proteins, including Pidd1, were captured by Neat1. Neat1 inhibited cell apoptosis and restricted inflammation by capturing Pidd1. The in vitro anti-apoptotic and anti-inflammatory effects of Neat1 were further confirmed in C57BL/6 mice, which resulted in better motor and cognitive function after TBI., Conclusion: Bexarotene up-regulates the lncRNA Neat1, which inhibits apoptosis and inflammation, thereby resulting in better functional recovery in mice after TBI., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The blood-tumor barrier (BTB) constitutes an efficient organization of tight junctions that limits the delivery of chemotherapeutic drugs to brain tumor tissues and impacts the treatment of glioma. Long non-coding RNAs (lncRNAs) are non-protein coding RNAs regulating gene expression, some lncRNAs play a crucial role in BTB permeability. However, the function of lncRNAs in BTB permeability is still largely unclear. Here, we have identified lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1), was remarkably up-regulated in glioma endothelial cells (GECs) obtained from an in vitro BTB model. Knockdown of NEAT1 impaired the integrity and increased the permeability of the BTB, accompanied by downregulation of expression of the tight junction proteins ZO-1, occludin and claudin-5 in GECs. Both bioinformatics data and results of luciferase reporter assays demonstrated that NEAT1 influenced BTB permeability by binding to miR-181d-5p. Knockdown of NEAT1 also down-regulated the expression of sex determining region Y-box protein 5 (SOX5), which was defined as a direct and functional downstream target of miR-181d-5p. SOX5 interacts with the promoter region of ZO-1, occludin and claudin-5 in GECs. In conclusion, knockdown of NEAT1 increased BTB permeability by binding to miR-181d-5p and then reducing tight junction protein expression by targeting SOX5. These results suggest an important role for NEAT1 in regulating BTB permeability and provide an additional strategy for treating glioma., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Nuclear enriched abundant transcript 1 (NEAT1), an important cancer-associated long non-coding RNA (lncRNA), contributes to the development and progression of several cancers. An increased expression of NEAT1 was observed in cancers including bladder cancer, lung cancer and breast cancer (BC). However, the exact effect of NEAT1 in BC progression and the underlying molecular mechanisms are still unknown up to now. Here, we investigated the detailed role of NEAT1 in human BC cell lines and clinical tumor samples in order to validate the function of this molecule. In our research, lncRNA-NEAT1 was specifically upregulated in BC cell lines and promoted BC cell growth through targeting miR-101. Knockdown of NEAT1 inhibited the proliferation and DNA synthesis of human BC cell in vitro. In addition, the regulation of EZH2 by miR-101 was required in NEAT1 induced BC cell growth. These findings indicated that NEAT1 might suppress the tumor growth via miR-101 dependent EZH2 regulation. Taken together, our data indicated that NEAT1 might be an oncogenic lncRNA that promoted proliferation of BC and could be regarded as a therapeutic target in human BC., (Copyright © 2017 Elsevier Inc. All rights reserved.)

While most long noncoding RNAs (lncRNAs) appear indistinguishable from mRNAs, having 5' cap structures and 3' poly(A) tails, recent work has revealed new formats. Rather than taking advantage of the canonical cleavage and polyadenylation for their 3' end maturation, such lncRNAs are processed and stablized by a number of other mechanisms, including the RNase P cleavage to generate a mature 3' end, or capped by snoRNP complexes at both ends, or by forming circular structures. Importantly, such lncRNAs have also been implicated in gene expression regulation in mammalian cells. Here, we highlight recent progress in our understanding of the biogenesis and function of lncRNAs without a poly(A) tail. This paper is part of a directed issue entitled: The Non-coding RNA Revolution., (Copyright © 2013 Elsevier Ltd. All rights reserved.)