Noncoding RNA Nuclear-enriched Abundant Transcript Research Articles

The Implications of the Long Non-Coding RNA NEAT1 in Non-Cancerous Diseases.

Long non-coding RNAs (lncRNAs) are involved in a variety of biological and cellular processes as well as in physiologic and pathophysiologic events. This review summarizes recent literature about the role of the lncRNA nuclear enriched abundant transcript 1 (NEAT1) in non-cancerous diseases with a special focus on viral infections and neurodegenerative diseases. In contrast to its role as competing endogenous RNA (ceRNA) in carcinogenesis, NEAT1’s function in non-cancerous diseases predominantly focuses on paraspeckle-mediated effects on gene expression. This involves processes such as nuclear retention of mRNAs or sequestration of paraspeckle proteins from specific promoters, resulting in transcriptional induction or repression of genes involved in regulating the immune system or neurodegenerative processes. NEAT1 expression is aberrantly—mostly upregulated—in non-cancerous pathological conditions, indicating that it could serve as potential prognostic biomarker. Additional studies are needed to elucidate NEAT1’s capability to be a therapeutic target for non-cancerous diseases.

Long Noncoding RNA NEAT1 Aggravates Aβ-Induced Neuronal Damage by Targeting miR-107 in Alzheimer's Disease.

PurposeAlzheimer's disease (AD) is the most common neurodegenerative disease, with a rising prevalence worldwide. Long noncoding RNAs (lncRNAs) have been found to play important roles in the development and treatment of AD. However, the exact role of lncRNA nuclear enriched abundant transcript 1 (NEAT1) in neuronal damage in AD is largely unknown.Materials and MethodsThe AD model was established in SH-SY5Y and SK-N-SH cells via treatment with amyloid β1−42 (Aβ). The expression of NEAT1 and microRNA-107 (miR-107) was measured by quantitative real-time polymerase chain reaction. Cell viability and apoptosis were detected by MTT assay, immunocytochemistry, and flow cytometry. The expression of phosphorylated tau protein (p-Tau) was measured by Western blot. The interaction between NEAT1 and miR-107 was explored by bioinformatics analysis, luciferase activity, and RNA immunoprecipitation assays.ResultsNEAT1 expression was enhanced in Aβ-treated SH-SY5Y and SK-N-SH cells, and its knockdown attenuated Aβ-induced inhibition of viability and promotion of apoptosis and p-Tau levels. NEAT1 was indicated as a decoy of miR-107. miR-107 abundance was reduced in Aβ-treated cells, and its overexpression reversed Aβ-induced injury. Moreover, interference of miR-107 abated silencing of NEAT1-mediated inhibition of neuronal damage in Aβ-treated SH-SY5Y and SK-N-SH cells.ConclusionLncRNA NEAT1 aggravated Aβ-induced neuronal damage by sponging miR-107, indicating a novel avenue for treatment of AD.

Long noncoding RNA NEAT1 accelerates the proliferation and fibrosis in diabetic nephropathy through activating Akt/mTOR signaling pathway.

Accumulating evidence has indicated the significant roles of long noncoding RNAs (lncRNAs) in the pathophysiology of diabetic nephropathy (DN). LncRNA nuclear enriched abundant transcript 1 (NEAT1) has been reported to exert a key role in the progression of several diseases including diabetes. However, the role of NEAT1 in the regulation of DP progression remains barely known. Therefore, our study aimed to investigate the role of NEAT1 in a streptozotocin-induced diabetes model (DM) of rats and glucose-induced mouse mesangial cell models. Currently, we found that NEAT1 was greatly upregulated in DM rats and glucose-induced mice mesangial cells, in which a high activation of Akt/mTOR signaling was also observed. Then, it was shown that knockdown of NETA1 was able to reduce renal injury in DM rats obviously. In addition, cell counting kit-8 assay and 5-ethynyl-2'-deoxyuridine assay were carried out and we observed downregulation of NEAT1 significantly inhibited mesangial cell proliferation. Meanwhile, extracellular matrix proteins and messenger RNA (transforming growth factor β1, fibronectin, and collagen IV) expression was dramatically restrained by silencing of NEAT1 in the high glucose-induced mesangial cells. Finally, knockdown of NEAT1 greatly reduced the expression of the phosphorylation of Akt and mammalian target of rapamycin (mTOR) in vitro. These findings revealed that the decrease of NEAT1 repressed the proliferation and fibrosis in DN via activating the Akt/mTOR signaling pathway, which might represent a novel pathological mechanism of DN progression.

The long noncoding RNA NEAT1 and nuclear paraspeckles are up-regulated by the transcription factor HSF1 in the heat shock response

The long noncoding RNA (lncRNA) NEAT1 (nuclear enriched abundant transcript 1) is the architectural component of nuclear paraspeckles, and it has recently gained considerable attention as it is abnormally expressed in pathological conditions such as cancer and neurodegenerative diseases. NEAT1 and paraspeckle formation are increased in cells upon exposure to a variety of environmental stressors and believed to play an important role in cell survival. The present study was undertaken to further investigate the role of NEAT1 in cellular stress response pathways. We show that NEAT1 is a novel target gene of heat shock transcription factor 1 (HSF1) and is up-regulated when the heat shock response pathway is activated by sulforaphane (SFN) or elevated temperature. HSF1 binds specifically to a newly identified conserved heat shock element in the NEAT1 promoter. In line with this, SFN induced the formation of NEAT1-containing paraspeckles via an HSF1-dependent mechanism. HSF1 plays a key role in the cellular response to proteotoxic stress by promoting the expression of a series of genes, including those encoding molecular chaperones. We have found that the expression of HSP70, HSP90, and HSP27 is amplified and sustained during heat shock in NEAT1-depleted cells compared with control cells, indicating that NEAT1 feeds back via an unknown mechanism to regulate HSF1 activity. This interrelationship is potentially significant in human diseases such as cancer and neurodegenerative disorders.

Long noncoding RNA NEAT1 promotes cell proliferation, migration, and invasion in hepatocellular carcinoma through interacting with miR-384.

It was reported that long non‐coding RNA nuclear‐enriched abundant transcript 1 (NEAT1) is involved in hepatocellular carcinoma (HCC). However, the underlying mechanism of tumorigenesis is still largely unclear. Here, we found that NEAT1 is remarkably upregulated in HCC tissues and cell lines. Overexpression of NEAT1 notably accelerated HCC cell proliferation, migration, and invasion. Knockdown of NEAT1 significantly inhibited HCC cell proliferation, migration and invasion. MiR‐384 expression was lower in HCC tissues and cell lines than adjacent nontumor tissues and L02 cell. MiR‐384 exhibited the functions of tumor‐suppressive. The expression of miR‐384 was negatively correlated with the expression of NEAT1. Overexpression of NEAT1 reduced miR‐384 expression, whereas inhibition of miR‐384 led to a distinct upregulation of NEAT1 expression. In addition, we provided evidence that miR‐384 was directly bound to the sequence of NEAT1 by luciferase reporter and RNA‐binding protein immunoprecipitation assays. Overexpression of miR‐384 inhibited NEAT1 function. Thus, we demonstrated that NEAT1 promotes the malignant biological properties of hepatocellular carcinoma by negatively regulating miR‐384.

Long non-coding RNA NEAT1 promotes colorectal cancer progression by competitively binding miR-34a with SIRT1 and enhancing the Wnt/β-catenin signaling pathway

In recent years, accumulating evidence has indicated that long non-coding RNAs (lncRNAs) are powerful factors influencing the progression of multiple malignancies. Although a relationship between the lncRNA NEAT1 (nuclear enriched abundant transcript 1) and colorectal cancer has previously been reported, the functional mechanism underlying the involvement of NEAT1 in colorectal cancer remains unknown. In this study, we report that NEAT1 expression is up-regulated in colorectal cancer tissues, which correlates with advanced clinical features, poor overall survival and disease free survival. Up-regulated NEAT1 promotes cell proliferation and metastasis of colorectal cancer both in vitro and in vivo. Moreover, NEAT1 functions as an oncogene influencing cell viability and invasion in part by serving as a competing endogenous RNA (ceRNAs) modulating miRNA-34a expression, leading to subsequent repression of the miR-34a/SIRT1 axis and activation of the Wnt/β-catenin signaling pathway. Taken together, our study demonstrates that the lncRNA NEAT1 may serve as a prognostic biomarker and a potential therapeutic target in colorectal cancer.

Genome-wide screening of NEAT1 regulators reveals cross-regulation between paraspeckles and mitochondria.

The long noncoding RNA NEAT1 (nuclear enriched abundant transcript 1) nucleates the formation of paraspeckles, which constitute a type of nuclear body with multiple roles in gene expression. Here we identify NEAT1 regulators using an endogenous NEAT1 promoter-driven enhanced green fluorescent protein reporter in human cells coupled with genome-wide RNAi screens. The screens unexpectedly yield gene candidates involved in mitochondrial functions as essential regulators of NEAT1 expression and paraspeckle formation. Depletion of mitochondrial proteins and treatment of mitochondrial stressors both lead to aberrant NEAT1 expression via ATF2 as well as altered morphology and numbers of paraspeckles. These changes result in enhanced retention of mRNAs of nuclear-encoded mitochondrial proteins (mito-mRNAs) in paraspeckles. Correspondingly, NEAT1 depletion has profound effects on mitochondrial dynamics and function by altering the sequestration of mito-mRNAs in paraspeckles. Overall, our data provide a rich resource for understanding NEAT1 and paraspeckle regulation, and reveal a cross-regulation between paraspeckles and mitochondria.

The lncRNA NEAT1 activates Wnt/\u03b2-catenin signaling and promotes colorectal cancer progression via interacting with DDX5

BackgroundThe long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) has been reported to be overexpressed in colorectal cancer (CRC). However, its underlying mechanisms in the progression of CRC have not been well studied.MethodsTo investigate the clinical significance of NEAT1, we analyzed its expression levels in a publicly available dataset and in 71 CRC samples from Fudan University Shanghai Cancer Center. Functional assays, including the CCK8, EdU, colony formation, wound healing, and Transwell assays, were used to determine the oncogenic role of NEAT1 in human CRC progression. Furthermore, RNA pull-down, mass spectrometry, RNA immunoprecipitation, and Dual-Luciferase Reporter Assays were used to determine the mechanism of NEAT1 in CRC progression. Animal experiments were used to determine the role of NEAT1 in CRC tumorigenicity and metastasis in vivo.ResultsNEAT1 expression was significantly upregulated in CRC tissues compared with its expression in normal tissues. Altered NEAT1 expression led to marked changes in proliferation, migration, and invasion of CRC cells both in vitro and in vivo. Mechanistically, we found that NEAT1 directly bound to the DDX5 protein, regulated its stability, and sequentially activated Wnt signaling. Our study showed that NEAT1 indirectly activated the Wnt/β-catenin signaling pathway via DDX5 and fulfilled its oncogenic functions in a DDX5-mediated manner. Clinically, concomitant NEAT1 and DDX5 protein levels negatively correlated with the overall survival and disease-free survival of CRC patients.ConclusionsOur findings indicated that NEAT1 activated Wnt signaling to promote colorectal cancer progression and metastasis. The NEAT1/DDX5/Wnt/β-catenin axis could be a potential therapeutic target of pharmacological strategies.

Long non-coding RNA nuclear-enriched abundant transcript 1 inhibition blunts myocardial ischemia reperfusion injury via autophagic flux arrest and apoptosis in streptozotocin-induced diabetic rats

Background and aimsThis 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. MethodsScreening 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. ResultsNeat1 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. ConclusionsI/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.

Resveratrol inhibits proliferation, migration and invasion of multiple myeloma cells via NEAT1-mediated Wnt/β-catenin signaling pathway

PurposeTo study the influence of resveratrol on proliferation, migration and invasion of multiple myeloma (MM) cells through the long noncoding RNA (lncRNA) NEAT1 (nuclear enriched abundant transcript 1)-modulated Wnt/β-catenin signaling pathway. MethodsMicroarray analysis was used to screen aberrantly expressed lncRNAs from MM cells and normal plasmocytes. The effects of NEAT1 overexpression/silencing or resveratrol treatment on MM cell (U266 and LP1) proliferation, migration and invasion were investigated using CCK-8 (Cell Counting Kit-8), wound healing and Transwell invasion assays. Expression of Wnt/β-catenin related proteins and unfolded protein response (UPR)-related proteins was detected by western blot. ResultslncRNA NEAT1 was highly expressed in MM cells, which could be significantly inhibited by resveratrol. NEAT1 overexpression induced proliferation, migration and invasion of MM cells, while resveratrol counteracted its effect. NEAT1 upregulated protein expression in the Wnt/β-catenin signaling pathway, while resveratrol reversed the negative effect of NEAT1 overexpression on MM cells through the Wnt/β-catenin signaling pathway, and hence suppressed MM cell reproduction, migration and invasion. Resveratrol could also restrain unfolded protein response in MM cells. ConclusionResveratrol downregulated the expression of lncRNA NEAT1 in MM cells and inhibited proliferation, migration and invasion of MM cells by suppressing the Wnt/β-catenin signaling pathway and unfolded protein response.

Oncogenic Properties of NEAT1 in Prostate Cancer Cells Depend on the CDC5L-AGRN Transcriptional Regulation Circuit.

The long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) has been shown to regulate multiple cancer-related cellular activities including cell proliferation, apoptosis, and migration. In this study, we confirm that repression of NEAT1 induces DNA damage, disturbs the cell cycle, and arrests the proliferation of prostate cancer cells. By taking advantage of the prostate cancer tumor transcriptome profiles from The Cancer Genome Atlas, our data-mining pipeline identified a series of transcription factors (TF) whose regulatory activities on target genes depended on the level of NEAT1. Among them was putative TF CDC5L, which bound directly to NEAT1. Silencing NEAT1 in prostate cancer cells repressed the transcriptional activity of CDC5L, and RNA-seq and ChIP-seq analyses further revealed a handful of potential targets of CDC5L regulated by NEAT1 expression. One target of CDC5L, ARGN, mediated the strong phenotypic consequences of NEAT1 reduction, including DNA damage, cell-cycle dysregulation, and proliferation arrest. In summary, we have established the requirement of the CDC5L-AGRN circuit for the essential oncogenic role of NEAT1 in prostate cancer cells.Significance: An integrative methodology uncovers CDC5L-AGRN signaling as critical to the tumor-promoting function of long noncoding RNA NEAT1 in prostate cancer cells. Cancer Res; 78(15); 4138-49. ©2018 AACR.

Long non-coding RNA NEAT1 promotes migration and invasion of oral squamous cell carcinoma cells by sponging microRNA-365.

Long non-coding RNA nuclear enriched abundant transcript 1 (NEAT1) has been demonstrated to serve key roles in numerous human cancer types, but its function in oral squamous cell carcinoma (OSCC) and underlying regulatory mechanism have not been evaluated. The present study demonstrated that expression of NEAT1 was significantly higher in OSCC tissue and cell lines compared with adjacent non-tumour tissue and normal oral keratinocytes, respectively. Additionally, upregulation of NEAT1 was significantly associated with advanced clinical stage and shorter survival time in patients with OSCC. Bioinformatics analysis and luciferase reporter gene assay data confirmed the interaction between NEAT1 and miR-365, and it was revealed that NEAT1 may downregulate microRNA (miR)-365 expression in OSCC cells. Furthermore, inhibition of NEAT1 expression led to a significant reduction in OSCC cell migration and invasion, which was accompanied by reduced matrix metalloproteinase (MMP)-2 and MMP9 protein expression. By contrast, inhibition of miR-365 eliminated suppressive effects of NEAT1 knockdown on OSCC cell migration and invasion. miR-365 was significantly downregulated in OSCC tissue and cell lines and an inverse correlation between miR-365 and NEAT1 expression in OSCC tissue was observed. To conclude, the present study demonstrated that NEAT1 promoted migration and invasiveness of OSCC cells by sponging miR-365. The current study suggests that NEAT1 may serve as a novel therapeutic target for the treatment of OSCC.

Long non-coding RNA NEAT1 promotes viability and migration of gastric cancer cell lines through up-regulation of microRNA-17.

Gastric carcinoma (GC) is a common cancer with heavy mortality and poor outcome at advanced stages and metastasis. Long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) has been reported to be an oncogene in GC recently. However, the underlying mechanism is far from understood. We aimed to explore the role of NEAT1 in GC as well as the underlying mechanisms. The expression of NEAT1 in clinical human GC tissues and GC cell lines were assessed by quantitative reverse transcription PCR. Then, NEAT1 was non-physiologically expressed in GC cells (SGC-7901 and MKN45 cells), followed by estimation of cell viability, migration, invasion, apoptosis, activation of the phosphatidylinositol-3-kinase (PI3K)/AKT and glycogen synthase kinase 3β (GSK3β) pathways, and microRNA (miR)-17 level. Moreover, the effects of miR-17 inhibition on cell viability, migration, and activation of the PI3K/AKT and GSK3β pathways in GC cells overexpressing NEAT1 were also explored. NEAT1 was up-regulated in GC tissues and cell lines. Then, cell viability and migration of GC cells were markedly increased by NEAT1 overexpression, while the cell invasion and apoptosis were unchanged. The phosphorylated level of PI3K, AKT, and GSK3β were increased by NEAT1 overexpression. Subsequently, we found miR-17 level was positively correlated with NEAT1 expression, and NEAT1 functions through up-regulating miR-17. NEAT1 was up-regulated in GC tissues and cell lines. Its overexpression enhanced cell viability and migration through up-regulating miR-17, along with activation of the PI3K/AKT and GSK3β pathways.

Long non-coding RNA NEAT1 promoted ovarian cancer cells' metastasis through regulation of miR-382-3p/ROCK1 axial.

Long non‐coding RNA (lncRNA) are extensively involved in various malignant tumors, including ovarian cancer (OC). In the present study, we focused on the expression and function of nuclear enriched abundant transcript 1 (NEAT1) in OC cells’ metastasis. We demonstrated that NEAT1 was upregulated in OC tissue specimens and cell lines. In addition, we revealed that depression of NEAT1 inhibited OC cells’ metastasis and the expression of Rho associated coiled‐coil containing protein kinase 1 (ROCK1), which is a metastasis‐related gene. Using online predictive software and a series of luciferase assays, we demonstrated that both NEAT1 and ROCK1 were the targets of microRNA‐382‐3p (miR‐382‐3p) and share similar microRNA responding elements (MRE). Furthermore, we illustrated that NEAT1 and miR‐382‐3p inhibited each other in a reciprocal manner. Finally, through antisense experiments we demonstrated that NEAT1 promoted ROCK1‐mediated metastasis by functioning as a ceRNA of miR‐382‐3p. In summary, the findings of this study revealed that NEAT1 promoted OC cells’ metastasis through regulating the miR‐382‐3p/ROCK1 axial. The present study might provide a new target for treating OC.

Circulating lncRNA NEAT1 correlates with increased risk, elevated severity and unfavorable prognosis in sepsis patients

ObjectiveTo investigate the correlation of circulating long non-coding RNA nuclear-enriched abundant transcript 1 (lncRNA NEAT1) expression with disease risk, severity, prognosis and inflammatory cytokine levels in sepsis patients. Methods152 sepsis patients and 150 health controls (HCs) were enrolled in this study. Plasma and serum samples were obtained from sepsis patients and HCs, and lncRNA NEAT1 expression in plasma was determined by quantitative polymerase chain reaction, while levels of inflammatory cytokines in serum were detected by enzyme linked immune sorbent assay. ResultsLncRNA NEAT1 expression was remarkably higher in sepsis patients than in HCs (P < 0.001). Receiver operating characteristic (ROC) curve disclosed a good predictive value of lncRNA NEAT1 expression for sepsis risk with area under curve (AUC) of 0.730 (95% CI: 0.740–0.861). Subsequent multivariate logistic regression analysis demonstrated that lncRNA NEAT1 expression was independently associated with higher sepsis risk (P < 0.001). In sepsis patients, lncRNA NEAT1 expression was also observed to be positively correlated with Acute Physiology and Chronic Health Evaluation (APACHE) II score (P < 0.001), serum tumor necrosis factor-α (P < 0.001), interleukin (IL)-1β (P = 0.043), IL-6 (P = 0.001) and IL-8 (P = 0.038), while negatively correlated with IL-10 (P < 0.001). In addition, lncRNA NEAT1 expression was increased in non-survivors compared to survivors (P = 0.006), and ROC curve revealed a good prognostic value of lncRNA NEAT1 for non-survivor risk with AUC 0.641 (95% CI: 0.536–0.746). ConclusionCirculating lncRNA NEAT1 correlates with increased disease risk, elevated severity and unfavorable prognosis as well as higher expression of pro-inflammatory cytokines in sepsis patients.

The long noncoding RNA NEAT1 contributes to hepatocellular carcinoma development by sponging miR-485 and enhancing the expression of the STAT3.

Accumulating evidence has supported the significance of lncRNAs in tumorigenesis. Recently, some studies indicate the oncogenic role of lncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) in hepatocellular carcinoma (HCC). In our present study, we focused on the biological mechanisms through which NEAT1 can regulate HCC development. We found that NEAT1 was greatly upregulated in human HCC cell lines including Huh7, Hep3B, HepG2, Bel-7404, and SK-Hep1 cells compared to the normal human liver cell line LO2. In addition, we observed that miR-485 was significantly downregulated in HCC cells. It was implied that miR-485 was increased by sh-NEAT1 and miR-485 can modulate NEAT1 expression negatively. Meanwhile, NEAT1inhibiton can repress HCC growth, migration, and invasion capacity in HepG2 and Hep3B cells. Through performing bioinformatic analysis, dual-luciferase reporter test, RNA-binding protein immunoprecipitation, and RNA pull-down assay, miR-485 was confirmed as a interacting target of NEAT1. Additionally, STAT3 was recognized as a direct target of miR-485 and miR-485 mimics can inhibit STAT3 expression. It was demonstrated that NEAT1 can increase STAT3 levels while miR-485 mimics can repress STAT3. Moreover, we found that sh-STAT3 was able to restrain HCC cell migration and invasion process. NEAT1 can act as a competing endogenous lncRNA (ceRNA) to regulated STAT3 by sponging miR-485 in HCC. Taken these together, NEAT1 can be used as an important biomarker in HCC diagnosis and treatment.

Long non-coding RNA NEAT1 promotes proliferation, migration and invasion of human osteosarcoma cells.

Aim: Long non-coding RNAs (LncRNAs) have been identified to play a crucial role in tumorigenesis and the progression of many types of tumors. However, the clinical significance and biological function of lncRNA nuclear-enriched abundant transcript 1(NEAT1) in human osteosarcoma remains unknown. Here, we investigated the role of NEAT1 in human osteosarcoma cell lines and clinical tumor samples.Methods: In this study, expression of NEAT1 was analyzed in 19 osteosarcoma tissues and paired adjacent non-tumor tissues by using quantitative real-time PCR. Additionally, knockdown of NEAT1 expression using Lentivirus-mediated siRNA was performed in order to explore the biological function of NEAT1 on osteosarcoma cell proliferation and metastasis through MTT, colony formation assay and transwell assay.Results: NEAT1 was over-expressed in osteosarcoma tissues compared with adjacent non-tumor tissues. In addition, knockdown of NEAT1 expression could suppress cell proliferation, migration and invasion in vitro.Conclusion: LncRNA NEAT1 was up-regulated in osteosarcoma tissue, promoting proliferation and metastasis of osteosarcoma cells. These findings indicate the role of this substance, as a growth regulator in osteosarcoma, and thus it may serve as a novel biomarker, and drug target for developing osteosarcoma therapies.

Oncogenic non-coding RNA NEAT1 promotes the prostate cancer cell growth through the SRC3/IGF1R/AKT pathway.

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.

C/EBPβ contributes to transcriptional activation of long non-coding RNA NEAT1 during APL cell differentiation

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.

NEAT1 promotes cell proliferation and invasion in hepatocellular carcinoma by negative regulating miR-613 expression

BackgroundLong non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) was found to be participated in tumorigenesis in various cancers including hepatocellular carcinoma (HCC). However, the clinical implication and underling function of NEAT1 in HCC have not been fully known. MethodsThe relative NEAT1 expression was examined by qRT-PCR in HCC tissues and cells, compared with adjacent normal tissues and normal human hepatocyte (LO2) cells, respectively. Cell proliferation and invasion were examined by MTT, cell colony formation and transwell assays. Luciferase reporter assay was performed to verify miR-613 was a direct target of NEAT1. Western blot analysis was also performed. ResultsNEAT1 was notably upregulated in HCC tissues and cells. Higher NEAT1 expression associated with larger tumor size and vascular invasion of HCC patients. Knockdown of NEAT1 significantly suppressed HCC cell proliferation, colony formation and cell invasion. Interestingly, lower miR-613 expression negatively associated with the NEAT1 expression in HCC tissues and was regulated by NEAT1. Additionally, we demonstrated that NEAT1 promoted HCC cell proliferation and invasion by regulating miR-613 expression. ConclusionThese results implied that inhibition of NEAT1 may be a potential therapeutic strategy for HCC patients.