Long noncoding RNA NEAT1 promotes glioma pathogenesis by regulating miR-449b-5p/c-Met axis

Li, Zhen; Liu, Yunhui; Diao, Hongyan; Ma, Jun; Yao, Yongliang

doi:10.1007/s13277-015-3843-y

Cited by 149 publications

(120 citation statements)

References 36 publications

(35 reference statements)

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“…Although recent studies have indicated that NEAT1 can promote the growth and survival of in vitro-cultured cancer cells 33,34 and that high NEAT1 levels correlate with poor prognosis in various types of cancer [35][36][37] , our data establish the first clear genetic link between NEAT1 and carcinogenesis. Consistent with published reports 13 , we provide evidence that NEAT1 is a bona fide p53 target gene.…”

Section: Discussionmentioning

confidence: 61%

p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity

Adriaens

Standaert

Barra

et al. 2016

Nat Med

373

424

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In a search for mediators of the p53 tumor suppressor pathway, which induces pleiotropic and often antagonistic cellular responses, we identified the long noncoding RNA (lncRNA) NEAT1. NEAT1 is an essential architectural component of paraspeckle nuclear bodies, whose pathophysiological relevance remains unclear. Activation of p53, pharmacologically or by oncogene-induced replication stress, stimulated the formation of paraspeckles in mouse and human cells. Silencing Neat1 expression in mice, which prevents paraspeckle formation, sensitized preneoplastic cells to DNA-damage-induced cell death and impaired skin tumorigenesis. We provide mechanistic evidence that NEAT1 promotes ATR signaling in response to replication stress and is thereby engaged in a negative feedback loop that attenuates oncogene-dependent activation of p53. NEAT1 targeting in established human cancer cell lines induced synthetic lethality with genotoxic chemotherapeutics, including PARP inhibitors, and nongenotoxic activation of p53. This study establishes a key genetic link between NEAT1 paraspeckles, p53 biology and tumorigenesis and identifies NEAT1 as a promising target to enhance sensitivity of cancer cells to both chemotherapy and p53 reactivation therapy.

show abstract

Section: Discussionmentioning

confidence: 61%

p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity

Adriaens

Standaert

Barra

et al. 2016

Nat Med

373

424

View full text Add to dashboard Cite

show abstract

“…We also found that MALAT1 and NEAT1 were highly expressed in GSCs. Although these are well known important functional lncRNAs associated with glioma behaviour143435, they did not appear to be involved in the Notch-induced GSC maintenance system (Supplementary Fig. 4f-h).…”

Section: Discussionmentioning

confidence: 96%

Targeting the Notch-regulated non-coding RNA TUG1 for glioma treatment

et al. 2016

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Targeting self-renewal is an important goal in cancer therapy and recent studies have focused on Notch signalling in the maintenance of stemness of glioma stem cells (GSCs). Understanding cancer-specific Notch regulation would improve specificity of targeting this pathway. In this study, we find that Notch1 activation in GSCs specifically induces expression of the lncRNA, TUG1. TUG1 coordinately promotes self-renewal by sponging miR-145 in the cytoplasm and recruiting polycomb to repress differentiation genes by locus-specific methylation of histone H3K27 via YY1-binding activity in the nucleus. Furthermore, intravenous treatment with antisense oligonucleotides targeting TUG1 coupled with a drug delivery system induces GSC differentiation and efficiently represses GSC growth in vivo. Our results highlight the importance of the Notch-lncRNA axis in regulating self-renewal of glioma cells and provide a strong rationale for targeting TUG1 as a specific and potent therapeutic approach to eliminate the GSC population.

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“…Numerous of lncRNAs have been evaluated, including lncRNA GAS5 [68, 69], and CCAT1 [70]. In our study, we investigated the effect of NEAT1 on NSCLC cells and discovered that NEAT1 involved in the ceRNA regulatory network and functioned as endogenous miRNA sponges to bind to miR-377-3p and regulated its function [71]. Recent studies indicated miR-377 showed tumor suppressive role on malignant melanoma [72], human clear cell renal cell carcinoma (CCRCC) [73], and hepatocellular carcinoma [74], while its role on NSCLC had not been investigated.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA NEAT1 promotes non-small cell lung cancer progression through regulation of miR-377-3p-E2F3 pathway

et al. 2016

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Recently, the long non-coding RNA (lncRNA) NEAT1 has been identified as an oncogenic gene in multiple cancer types and elevated expression of NEAT1 was tightly linked to tumorigenesis and cancer progression. However, the molecular basis for this observation has not been characterized in progression of non-small cell lung cancer (NSCLC). In our studies, we identified NEAT1 was highly expressed in patients with NSCLC and was a novel regulator of NSCLC progression. Patients whose tumors had high NEAT1 expression had a shorter overall survival than patients whose tumors had low NEAT1 expression. Further, NEAT1 significantly accelerates NSCLC cell growth and metastasis in vitro and tumor growth in vivo. Additionally, by using bioinformatics study and RNA pull down combined with luciferase reporter assays, we demonstrated that NEAT1 functioned as a competing endogenous RNA (ceRNA) for hsa-miR-377-3p, antagonized its functions and led to the de-repression of its endogenous targets E2F3, which was a core oncogene in promoting NSCLC progression. Taken together, these observations imply that the NEAT1 modulated the expression of E2F3 gene by acting as a ceRNA, which may build up the missing link between the regulatory miRNA network and NSCLC progression.

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Long noncoding RNA NEAT1 promotes glioma pathogenesis by regulating miR-449b-5p/c-Met axis

Cited by 149 publications

References 36 publications

p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity

p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity

Targeting the Notch-regulated non-coding RNA TUG1 for glioma treatment

Long non-coding RNA NEAT1 promotes non-small cell lung cancer progression through regulation of miR-377-3p-E2F3 pathway

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