Long non-coding RNA NEAT1 shows high expression unrelated to molecular features and clinical outcome in multiple myeloma.
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ABSTRACT:
SUBMITTER: Taiana E
PROVIDER: S-EPMC6355474 | biostudies-literature | 2019 Feb
REPOSITORIES: biostudies-literature
Publications
Long non-coding RNA NEAT1 shows high expression unrelated to molecular features and clinical outcome in multiple myeloma.
Taiana Elisa E Ronchetti Domenica D Favasuli Vanessa V Todoerti Katia K Manzoni Martina M Amodio Nicola N Tassone Pierfrancesco P Agnelli Luca L Neri Antonino A
Haematologica 20180913 2
Similar Datasets
Project description:Multiple myeloma (MM) is a malignant proliferation of bone marrow plasma cells, whose pathogenesis remains largely unknown. Long ncRNAs (lncRNAs) are a large class of non-protein-coding RNA, involved in many physiological cellular and genomic processes as well as in carcinogenesis, cancer metastasis and invasion. The biological role and therapeutic potential of lncRNAs in MM are still to be explored. Herein, we investigated the nuclear paraspeckle assembly transcript 1 (NEAT1) in the context of plasma cell dyscrasia, in a cohort of 50 MM and 15 plasma cell leukemia samples. Array expression data indicated that NEAT1 was upregulated in tumor samples compared to four healthy controls. Moreover, in MM patients, NEAT1 was globally overexpressed irrespectively of molecular characteristic, as further supported by Q-RT-PCR validation and by RNA sequencing data in a representative subgroup of cases. The functional annotation of genes and the lncRNAs transcriptional signature associated with NEAT1 expression indicated the modulation of DNA repair and metabolism, dynein interaction and unfolded protein response pathways. We tested NEAT1 clinical relevance in a retrospective proprietary dataset including 55 MM and in the large TT2/TT3 trials cohort from the University of Arkansas encompassing more than 550 patients; in both cases, NEAT1 overexpression was not correlated with patient’s prognosis.
2019-06-18 | GSE116294 | GEO
Project description:BackgroundThe present study aimed to explore the association of long non-coding RNA nuclear paraspeckle assembly transcript 1 (lncRNA NEAT1) with multiple myeloma (MM) risk and further investigate its correlation with clinical features, treatment response, survival profiles, and its interaction with microRNA-125a (miR-125a) in MM patients.MethodsTotally, 114 de novo symptomatic MM patients and 30 healthy donors (as controls) were recruited. Their bone marrow samples were collected before treatment (MM patients) and at enrollment (healthy donors), respectively. Subsequently, plasma cells were isolated from bone marrow for detection of lncRNA NEAT1 and miR-125a expression via reverse transcription quantitative polymerase chain reaction.ResultslncRNA NEAT1 was upregulated in MM patients compared with healthy donors and presented with excellent value in distinguishing MM patients from healthy donors. In MM patients, lncRNA NEAT1 positively associated with International Staging System (ISS) stage, beta-2 microglobulin (β2-MG), and lactate dehydrogenase (LDH), but not correlated with core cytogenetics and other clinical features. Furthermore, lncRNA NEAT1 negatively associated with complete remission (CR), overall remission rate (ORR), progression-free survival (PFS), and overall survival (OS). Moreover, lncRNA NEAT1 negatively associated with miR-125a in MM patients. MiR-125a was downregulated in MM patients compared with healthy donors, and it negatively associated with ISS stage, β2-MG, and LDH, but positively correlated with CR, ORR, PFS, and OS in MM patients.ConclusionlncRNA NEAT1 might interact with miR-125a, and serves as a novel biomarker for treatment response and survival profiles in MM, indicating its clinical value for MM management.
| S-EPMC7521229 | biostudies-literature
Project description:Deregulated high expression of NEAT1 lncRNA in multiple myeloma is unrelated to molecular features and clinical outcome
| PRJNA478041 | ENA
Project description:BackgroundThis study aimed to investigate the correlation of long non-coding RNA T-cell factor 7 (lnc-TCF7) with clinical features and prognosis in patients with multiple myeloma (MM).MethodsTotally, 216 newly diagnosed symptomatic MM patients and 60 healthy controls (HCs) were enrolled. Bone marrow samples were collected from patients before treatment and from HCs on donation to detect lnc-TCF7 expression in plasma cells by reverse transcription quantitative polymerase chain reaction. Besides, clinical response, progression-free survival (PFS), and overall survival (OS) of patients were assessed.ResultsLnc-TCF7 expression was increased in patients with MM compared with HCs. Lnc-TCF7 expression was highest in international staging system (ISS) stage III patients, followed by ISS stage II patients, and then ISS stage I patients, while lnc-TCF7 expression was similar in patients with different immunoglobulin subtypes and Durie-Salmon stages. Regarding chromosomal abnormalities, lnc-TCF7 expression positively correlated with t(4; 14) and Del(17p), whereas no correlation of lnc-TCF7 expression with t(14; 16), 1q21 amplification, Del(13q), or hyperdiploid was observed in patients with MM. Furthermore, lnc-TCF7 expression positively correlated with serum creatinine, beta-2-microglobulin, and lactate dehydrogenase in patients. Besides, lnc-TCF7 was negatively associated with complete response but not overall response rate in patients. Additionally, patients with lnc-TCF7 high expression exhibited shorter PFS and OS compared to patients with lnc-TCF7 low expression.ConclusionLnc-TCF7 might have clinical value in aiding disease management and prognosis prediction of MM.
| S-EPMC7521284 | biostudies-literature
Project description:Background:Long non-coding RNA (lncRNA) BM742401 is a tumor suppressor in gastric cancer and chronic lymphocytic leukemia. As the promoter and coding region of BM742401 are fully embedded in a CpG island, we hypothesized that BM742401 is a tumor suppressor lncRNA epigenetically silenced by promoter DNA methylation in multiple myeloma. Methods:Methylation-specific PCR and quantitative bisulfite pyrosequencing were performed to detect the methylation of BM742401 in normal plasma cells, myeloma cell lines and primary myeloma samples. The expression of BM742401 was measured by qRT-PCR. The function of BM742401 in multiple myeloma cells was analyzed by lentivirus transduction followed by migration assay. Results:BM742401 methylation was detected in 10 (66.7%) myeloma cell lines but not normal plasma cells, and inversely correlated with expression of BM742401. In primary samples, BM742401 methylation was detected in 3 (12.5%) monoclonal gammopathy of undetermined significance, 9 (15.8%) myeloma at diagnosis and 8 (17.0%) myeloma at relapse/progression. Moreover, BM742401 methylation at diagnosis was associated with inferior overall survival (median OS: 25 vs. 39 months; P?=?0.0496). In myeloma cell line JJN-3, stable overexpression of BM742401 by lentivirus transduction resulted in reduced cell migration (P?=?0.0001) but not impacting cell death or proliferation. Conclusions:This is the first report of tumor-specific methylation-mediated silencing of BM742401 in myeloma, which is likely an early event in myelomagenesis with adverse impact on overall survival. Moreover, BM742401 is a tumor suppressor lncRNA by inhibiting myeloma cell migration, hence implicated in myeloma plasma cell homing, metastasis and disease progression.
| S-EPMC7446116 | biostudies-literature
Project description:The identification of deregulated microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in multiple myeloma (MM) has progressively added a further level of complexity to MM biology. In addition, the cross-regulation between lncRNAs and miRNAs has begun to emerge, and theoretical and experimental studies have demonstrated the competing endogenous RNA (ceRNA) activity of lncRNAs as natural miRNA decoys in pathophysiological conditions, including cancer. Currently, information concerning lncRNA and miRNA interplay in MM is virtually absent. Herein, we investigated in silico the lncRNA and miRNA relationship in a representative datasets encompassing 95 MM and 30 plasma cell leukemia patients at diagnosis and in four normal controls, whose expression profiles were generated by a custom annotation pipeline to detect specific lncRNAs. We applied target prediction analysis based on miRanda and RNA22 algorithms to 235 lncRNAs and 459 miRNAs selected with a potential pivotal role in the pathology of MM. Among pairs that showed a significant correlation between lncRNA and miRNA expression levels, we identified 11 lncRNA-miRNA relationships suggestive of a novel ceRNA network with relevance in MM.
| S-EPMC5192483 | biostudies-literature
Project description:UNLABELLED:Hepatocellular carcinoma (HCC), a primary malignancy of the liver, is associated with high mortality rate and poor prognosis. Emerging evidence showed that novel biomarkers are required toward a better understanding of the biological mechanisms of HCC. NEAT1 (nuclear paraspeckle assembly transcript 1, also known as MEN?/?), a novel long non-coding RNA (lncRNA), serves as a crucial regulator in several cancers. However, the correlation between NEAT1 expression with tumorigenesis and metastasis in HCC tissues remains out of the question so far. In the current study, the aim was to evaluate the potential role of NEAT1 expression in HCC tissues and its relationship with clinicopathological parameters. METHOD:The expression of NEAT1 was detected by qRT-PCR, in 95 cases of adjacent non-cancerous liver and their paired HCC tissues, respectively. The associations of NEAT1 with clinicopathological features and other biological factors were further analyzed. RESULT:Our results revealed that NEAT1 appeared to have higher expression in the HCC tissues, compared with the adjacent non-cancerous liver tissues. High levels of NEAT1 promoted the clinical features of HCC, including the number of tumor nodes, metastasis, clinical TNM stage, the status of portal vein tumor embolus, vaso-invasion and the infiltration of tumor cells. Additionally, high NEAT1 expression levels were significantly associated with the expression level of MDTH, NM23 and MALAT1. CONCLUSION:Our study demonstrates that NEAT1 acts as a pivotal player in tumorigenesis and metastasis of hepatocellular carcinoma.
| S-EPMC4503113 | biostudies-other
Project description:Changes in the abundance and activity of long non-coding RNAs (lncRNAs) have an important impact on the development of cancer. The nuclear paraspeckle assembly transcript 1 (NEAT1) has been reported to be overexpressed in many types of cancer since its discovery. However, inconsistencies exist as NEAT1 can also function as a tumor suppressor in certain types of cancer, such as acute promyelocytic leukemia. Here we systematically describe our current understanding of NEAT1 in tumor initiation and progression. First, we analyzed the expression patterns of NEAT1 in various normal tissues and malignant cancers using data from public data portals, the Genotype-Tissue Expression Project (GTEx) and the Cancer Genome Atlas (TCGA), together with recent progress in the study of NEAT1 in various types of cancer. Second, we discussed the functions and mechanisms of NEAT1 in modulating tumor activity. Then, the upstream transcription factors and downstream microRNA targets of NEAT1 in the transcription cascade of cancers were also summarized. These data highlight the emerging role of NEAT1 in tumorigenesis, and present promising targetable pathways and clinical opportunities for tumor prevention and classifications.
| S-EPMC6146416 | biostudies-literature
Project description:NEAT1 is a highly and ubiquitously expressed long non-coding RNA (lncRNA) which serves as an important regulator of cellular stress response. However, the physiological role of NEAT1 in the central nervous system (CNS) is still poorly understood. In the current study, we addressed this by characterising the CNS function of the Neat1 knockout mouse model (Neat1-/- mice), using a combination of behavioural phenotyping, electrophysiology and expression analysis. RNAscope® in situ hybridisation revealed that in wild-type mice, Neat1 is expressed across the CNS regions, with high expression in glial cells and low expression in neurons. Loss of Neat1 in mice results in an inadequate reaction to physiological stress manifested as hyperlocomotion and panic escape response. In addition, Neat1-/- mice display deficits in social interaction and rhythmic patterns of activity but retain normal motor function and memory. Neat1-/- mice do not present with neuronal loss, overt neuroinflammation or gross synaptic dysfunction in the brain. However, cultured Neat1-/- neurons are characterised by hyperexcitability and dysregulated calcium homoeostasis, and stress-induced neuronal activity is also augmented in Neat1-/- mice in vivo. Gene expression analysis showed that Neat1 may act as a weak positive regulator of multiple genes in the brain. Furthermore, loss of Neat1 affects alternative splicing of genes important for the CNS function and implicated in neurological diseases. Overall, our data suggest that Neat1 is involved in stress signalling in the brain and fine-tunes the CNS functions to enable adaptive behaviour in response to physiological stress.
| S-EPMC7256041 | biostudies-literature
Project description:Internal ribosome entry sites (IRESs) drive translation initiation during stress. In response to hypoxia, (lymph)angiogenic factors responsible for tissue revascularization in ischemic diseases are induced by the IRES-dependent mechanism. Here, we searched for IRES trans-acting factors (ITAFs) active in early hypoxia in mouse cardiomyocytes. Using knock-down and proteomics approaches, we show a link between a stressed-induced nuclear body, the paraspeckle, and IRES-dependent translation. Furthermore, smiFISH experiments demonstrate the recruitment of IRES-containing mRNA into paraspeckle during hypoxia. Our data reveal that the long non-coding RNA Neat1, an essential paraspeckle component, is a key translational regulator, active on IRESs of (lymph)angiogenic and cardioprotective factor mRNAs. In addition, paraspeckle proteins p54nrb and PSPC1 as well as nucleolin and RPS2, two p54nrb-interacting proteins identified by mass spectrometry, are ITAFs for IRES subgroups. Paraspeckle thus appears as a platform to recruit IRES-containing mRNAs and possibly host IRESome assembly. Polysome PCR array shows that Neat1 isoforms regulate IRES-dependent translation and, more widely, translation of mRNAs involved in stress response.
| S-EPMC9799981 | biostudies-literature