LncRNA NEAT1/miR-129/Bcl-2 signaling axis contributes to HDAC inhibitor tolerance in nasopharyngeal cancer.
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ABSTRACT:
SUBMITTER: Xue F
PROVIDER: S-EPMC7425502 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We aimed to explore the interaction among lncRNA MALAT1, miR-129 and SOX2. Besides, we would investigate the effect of MALAT1 on the proliferation of glioma stem cells and glioma tumorigenesis. Differentially expressed lncRNAs in glioma cells and glioma stem cells were screened out with microarray analysis. The targeting relationship between miR-129 and MALAT1 or SOX2 was validated by dual-luciferase reporter assay. The expressions of MALAT1, miR-129 and SOX2mRNA in both glioma non-stem cells and glioma stem cells were examined by qRT-PCR assay. The impact of MALAT1 and miR-129 on glioma stem cell proliferation was observed by CCK-8 assay, EdU assay and sphere formation assay. The protein expression of SOX2 was determined by western blot. The effects of MALAT1 and miR-129 on glioma tumour growth were further confirmed using xenograft mouse model. The mRNA expression of MALAT1 was significantly up-regulated in glioma stem cells compared with non-stem cells, while miR-129 was significantly down-regulated in glioma stem cells. MALAT1 knockdown inhibited glioma stem cell proliferation via miR-129 enhancement. Meanwhile, miR-129 directly targeted at SOX2 and suppressed cell viability and proliferation of glioma stem cells by suppressing SOX2 expression. The down-regulation of MALAT1 and miR-129 overexpression both suppressed glioma tumour growth via SOX2 expression promotion in vivo. MALAT1 enhanced glioma stem cell viability and proliferation abilities and promoted glioma tumorigenesis through suppressing miR-129 and facilitating SOX2 expressions.
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Project description:Retinoblastoma (RB) is the most common intraocular tumor in childhood. Long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NTAT1) has been reported to be related to RB progression. This study aims to study the molecular mechanism of NEAT1 in regulating cell cycle, proliferation, apoptosis, migration, and invasion in RB. The expression levels of NEAT1 and miR-3619-5p were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of LIM and SH3 domain protein 1 (LASP1) was measured by western blot. The proliferation of RB cells was analyzed by cell counting kit-8 (CCK-8) and cell colony formation assays. Cell migration and invasion were evaluated by transwell assay. Cell cycle and apoptosis were assessed by flow cytometry analysis. The association between miR-3619-5p and NEAT1 or LASP1 was predicted by starBase 3.0 database and identified by dual-luciferase reporter assay. The effects of NEAT1 knockdown on the tumor growth in vivo were detected by in vivo tumor formation assay. NEAT1 expression was dramatically up-regulated, and miR-3619-5p expression was obviously downregulated in RB tissues and cells compared with control groups. The protein level of LASP1 was obviously increased in RB tissues or cells relative to paracancerous normal tissues or cells, respectively. Functionally, NEAT1 silencing inhibited RB cell migration, invasion, and proliferation, whereas induced cell apoptosis and cell cycle arrest in RB; this phenomenon was partially abolished by miR-3619-5p inhibitor. Mechanistically, NEAT1 acted as a sponge of miR-3619-5p, and miR-3619-5p was associated with LASP1. In addition, NEAT1 knockdown decreased the volume and weight of RB tumor in vivo. Together, NEAT1 silencing repressed cell migration, invasion, and proliferation, whereas induced cell apoptosis and cycle arrest by sponging miR-3619-5p to inhibit LASP1 expression in RB cells. This study may provide a theoretical basis for RB therapy.
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Project description:BACKGROUND:Long noncoding RNAs (lncRNA) are important in the growth and metastasis of colon cancer. The objective of this study was to describe the potential role of lncRNA NEAT1 in the progression of colon cancer. METHODS:Quantitative real-time polymerase chain reaction was used for detecting NEAT1, miR-185-5p, and IGF2 in colon cancer cells and tissues. The potential diagnostic value of NEAT1 in colon cancer was analyzed with the receiver operating characteristic curve. Kaplan-Meier method was applied for evaluating the association between NEAT1 expression and the overall survival of osteosarcoma patients, whereas Transwell assay was introduced to examine the potential invasion and migration of colon cancer cells. In addition, the binding of NEAT1/IGF2 to miR-185-5p was confirmed by RNA pull-down and RNA-binding protein immunoprecipitation assays and dual-luciferase reporter gene assay. Finally, rescue experiments were conducted to confirm the role of NEAT1/miR-185-5p/IGF2 axis in colon cancer. RESULTS:Colon cancer patients with low NEAT1 expression presented with longer overall survival than those with high expression. The migration and invasion of colon cancer cells were considerably promoted by overexpressed NEAT1. Both NEAT1 and IGF2 bound to miR-185-5p. CONCLUSION:NEAT1 upregulate IGF2 expression through absorbing miR-185-5p to enhances the migration and invasion of colon cancer cells.
| S-EPMC7196445 | biostudies-literature
Project description:BackgroundLong non-coding RNAs (lncRNAs) have been indicated to play critical roles in gastric cancer (GC) tumorigenesis and progression. However, their roles in GC remain to be further elucidated.MethodsRT-qPCR and fluorescence in situ hybridzation (FISH) were conducted to detect the expression of lncRNA NEAT1 in GC tissues and cell lines. Gene Set Enrichment Analysis (GSEA) was performed to screen out potential phenotypes and pathways that NEAT1 may participate in. NEAT1-silenced AGS and MGC803 cells were constructed and a series of functional experiments to investigate the roles of NEAT1 in GC angiogenesis both in vitro and in vivo. RNA pull down and luciferase reporter assays were utilized to illustrate the mechanisms underlying the functions of NEAT1 in GC.ResultsWe observed that NEAT1 was upregulated in most GC specimens and cell lines. NEAT1 high was correlated with poor prognosis of GC patients. In vitro experiments showed that NEAT1 promoted GC angiogenesis by enhancing proliferation, migration, and tube formation ability of endothelial cells. Mechanism researches revealed that NEAT1 could competitively sponge miR-17-5p which targeted TGFβR2 directly. Subsequently, activate TGFβ/Smad pathway by following with upregulation of a series of classical proangiogenic factors especially VEGF.ConclusionThe study unveiled that the LncRNA NEAT1/miR-17-5p/TGFβR2 axis is a novel mechanism in GC angiogenesis. Disrupting this axis may be a potential strategy for GC treatment.
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Project description:BACKGROUND:Long noncoding RNAs (lncRNAs) have been reported to be important regulators in pathogenesis of human cancers, including nasopharyngeal carcinoma (NPC). Here, we mainly aimed to explore the mechanisms of LncRNA-SNHG5/ miR-1179/HMGB3 axis in NPC progression. METHODS:RT-qPCR and Western blot analysis were employed to detect mRNA and protein expressions. CCK-8, Transwell and dual luciferase reporter assays were applied to investigate functions of LncRNA-SNHG5/miR-1179/HMGB3 axis. RESULTS:Upregulation of lncRNA-SNHG5 and downregulation of miR-1179 were identified in NPC, which were associated with adverse clinical outcomes. Functionally, upregulation of lncRNA-SNHG5 and downregulation of miR-1179 accelerated NPC cell proliferation, migration and invasion. Furthermore, lncRNA-SNHG5 acted as a molecular sponge of miR-1179 in NPC. Besides that, upregulation of HMGB3 was found in NPC, and knockdown of HMGB3 restrained NPC progression. Moreover, HMGB3, a target of miR-1179, regulated NPC progression by mediating LncRNA-SNHG5/miR-1179 axis. CONCLUSION:LncRNA SNHG5 serves as a tumor promoter in NPC by sponging miR-1179 and upregulating HMGB3.
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Project description:LncRNA NEAT1 functions as an oncogene in multiple human cancers. However, its expression and role in fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA) remain unclear. Thus, we investigated the expression of NEAT1 in synovial tissues and FLSs in RA, to determine its role in the development of RA. Quantitative real-time polymerase chain reaction was used to measure the expression of NEAT1. FLS proliferation was evaluated using cell proliferation assays. Flow cytometry was used to analyze cell cycle progression and apoptosis in FLSs. Binding between NEAT1 and miR-410-3p was demonstrated by dual-luciferase assays. We found that NEAT1 was upregulated in synovial tissues and FLSs in RA. Upregulation of NEAT1 promoted cell proliferation, induced S-to G2/M phase transition, and suppressed apoptosis in RA FLSs. NEAT1 directly bound to and negatively modulated miR-410-3p expression, while positively regulating YinYang 1(YY1; a miR-410-3p target). Inhibiting miR-410-3p and upregulating YY1 partially restored the inhibitory role in cell viability induced by the depletion of NEAT1 in RA FLSs. Besides pro-proliferative and anti-apoptotic roles, upregulation of NEAT1 promoted migration, invasion, and inflammatory cytokines secretion in RA FLSs. Taken together, our results suggest that the NEAT1 may serve as a novel diagnostic and therapeutic target for patients with RA.
| S-EPMC7485383 | biostudies-literature
Project description:AimEpithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells is the key of the development of diabetic retinopathy (DR), and lncRNA NEAT1 could accelerate EMT in diabetic nephropathy. Meanwhile, as a diabetes susceptibility gene, whether sex-determining region Y-related (SRY) high-mobility group box 4 (SOX4) has relationship with lncRNA NEAT1 in DR remains unclear.MethodsFirstly, NEAT1, SOX4 and miR-204 were evaluated by qRT-PCR (quantitative reverse-transcriptase PCR) under high glucose condition. Then, cell viability, proliferation, migration and invasion were respectively detected by MTT, BrdU staining, wound healing and transwell assay after NEAT1 knockdown or miR-204 overexpression. Also, the EMT-related proteins were examined by western blot and cell immunofluorescence assay. In order to confirm the relationship between miR-204 and NEAT1 or SOX4, dual luciferase reporter gene assay was conducted. At the same time, the protein levels of SOX4 and EMT-related proteins were investigated by immunohistochemistry in vivo.ResultsHigh glucose upregulated NEAT1 and SOX4 and downregulated miR-204 in ARPE19 cells. NEAT1 knockdown or miR-204 overexpression inhibited the proliferation and EMT progression of ARPE19 cells induced by high glucose. NEAT1 was identified as a molecular sponge of miR-204 to increase the level of SOX4. The effect of NEAT1 knockdown on the progression of EMT under high glucose condition in ARPE19 cells could be reversed by miR-204 inhibitor. Also, NEAT1 knockdown inhibited retinal EMT in diabetic mice.ConclusionNEAT1 regulated the development of EMT in DR through miR-204/SOX4 pathway, which could provide reference for clinical prevention and treatment.
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Project description:Long noncoding RNAs (lncRNAs) are frequently precursor RNAs of microRNAs (miRNAs) or act as competing endogenous RNAs (ceRNAs) to interact with miRNAs. To better understand the shared impact of lncRNAs and miRNAs in the regulatory post-transcriptional network, we focused here on the relationships between (a) lncRNA H19 and miR-675, (b) NEAT1 and miR-204, and (c) HOTAIR and miR-331 in plasma of early breast cancer (BC) patients. We quantified each RNA in plasma samples of 63 BC patients and 10 healthy women by quantitative real-time PCR. In cell culture experiments, the influence of these noncoding RNAs (ncRNAs) on proliferation and apoptosis of BC cell line MCF-7 was examined. Plasma levels of H19 (P = 0.030), NEAT1 (P = 0.030), and miR-331 (P = 0.012) were deregulated in BC patients compared with healthy women. In both cohorts, the concentrations of H19 correlated with those of miR-675 (P = 0.0001). Higher H19 (P = 0.001) along with lower miR-675 (P = 0.007) levels and higher miR-204 (P = 0.017) along with lower NEAT1 (P = 0.030) levels were detected in plasma of HER2-positive patients compared with the other BC subgroups. Whereas the expression of HOTAIR was below the detection level, miR-331 levels correlated with nodal status (P = 0.002) and recurrence (P = 0.012). In cell culture experiments, a competitive impact on cell proliferation and apoptosis by these ncRNAs was also documented. Our findings describe a relationship of the plasma levels of H19/miR-675 and NEAT1/miR-204 in the different BC subtypes; in addition, they reveal an interplay between these lncRNAs and miRNAs in the regulatory network in MCF-7 cells, which should also be considered in the search for new diagnostic and therapeutic markers.
| S-EPMC6487715 | biostudies-literature
Project description:Recent findings have shown that lncRNA dysregulation is involved in many cancers, including osteosarcoma (OS). In a previous study, we reported a novel lncRNA, ODRUL, that could promote doxorubicin resistance in OS. We now report the function and underlying mechanism of ODRUL in regulating OS progression. We show that ODRUL is upregulated in OS tissues and cell lines and correlates with poor prognosis. ODRUL knockdown significantly inhibits OS cell proliferation, migration, invasion, and tumor growth in vitro and in vivo by decreasing matrix metalloproteinase (MMP) expression. A microarray screen combined with online database analysis showed that miR-3182 is upregulated and MMP2 is downregulated in sh-ODRUL-expressing MG63 cells and that miR-3182 harbors potential binding sites for ODRUL and the 3' UTR of MMP2 mRNA. In addition, miR-3182 expression and function are inversely correlated with ODRUL expression in vitro and in vivo. A luciferase reporter assay demonstrated that ODRUL could directly interact with miR-3182 and upregulate MMP2 expression via its competing endogenous RNA activity on miR-3182 at the posttranscriptional level. Taken together, our study has elucidated the role of oncogenic ODRUL in OS progression and may provide a new target in OS therapy.
| S-EPMC5628795 | biostudies-literature
Project description:BACKGROUND:Nasopharyngeal carcinoma (NPC), with distinct geographical distribution, has gathered public attention. Despite that radiotherapy and chemotherapy are applied to treat NPC, cell metastasis still cannot be avoided. Numerous works have elucidated that lncRNAs are essential players in the development of multiple cancers. LncRNA SNHG7 has been reported as a contributing factor in the occurrence of certain cancers, but its mechanism in NPC deserves further investigation. The purpose of the study is to figure out the role and molecular regulation mechanism of SNHG7 in NPC. METHODS:The role of SNHG7 in NPC was verified by CCK-8, colony formation, EdU staining, western blot and capase-3 assays. The interactions between SNHG7/ELAVL1 and miR-514a-5p were confirmed by RNA pull down, RT-qPCR, RIP and luciferase reporter assays. RESULTS:SNHG7 was upregulated in NPC cells, and absence of SNHG7 suppressed cell proliferation as well as promoted cell apoptosis in NPC. Furthermore, SNHG7 was confirmed to bind with miR-514a-5p and negatively modulate miR-514a-5p expression. Besides, miR-514a-5p was found to be able to bind with ELAVL1 and negatively regulate ELAVL1 mRNA and protein expressions. In the end, rescue assays demonstrated that the miR-514a-5p deficiency restored the NPC progression inhibited by SNHG7 silence, and ELAVL1 partly counteracted the restoration caused by miR-514a-5p inhibitor in HNE1 cells. CONCLUSIONS:LncRNA SNHG7 promotes the proliferation and migration of nasopharyngeal carcinoma by miR-514a-5p/ ELAVL1 axis.
| S-EPMC7202000 | biostudies-literature