Long noncoding RNA GAS5 regulates the proliferation, migration, and invasion of glioma cells by negatively regulating miR‐18a‐5p

Liu, Qian; Yu, Wei; Zhu, Shaojun; Cheng, Ke; Xu, Hong; Lv, Yalan; Long, Xuan; Ma, Lan; Huang, Juan; Sun, Shanquan; Wang, Kejian

doi:10.1002/jcp.26889

Cited by 67 publications

(58 citation statements)

References 50 publications

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“…Therefore, our data identified LINC00526 as a potential prognostic biomarker for glioma and suggested that ectopic expression of LINC00526 may be a potential therapeutic strategy for glioma. LncRNAs GAS5, NEAT1, GACAT3, CASC9, HMMR‐AS1, LINC00152, HOTAIRM1, AC003092.1, HOXD‐AS1, OIP5‐AS1, DANCR and so on have been reported to play oncogenic or tumour suppressive roles in glioma . Our study further proved the critical roles of lncRNAs in glioma and provided another candidate lncRNA for glioma prognosis and therapy.…”

Section: Discussionsupporting

confidence: 63%

Long non‐coding RNA LINC00526 represses glioma progression via forming a double negative feedback loop with AXL

Yan

et al. 2019

J Cellular Molecular Medi

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Glioma is the most common primary intracranial carcinoma with extremely poor prognosis. The significances of long non‐coding RNA (lncRNA) involved in glioma have been started revealed. However, the expression, roles and molecular mechanisms of most lncRNAs in glioma are still unknown. In this study, we identified a novel lncRNA LINC00526, which is significantly low expressed in glioma. Low expression of LINC00526 is correlated with aggravation and poor survival in glioma. Functional assays revealed that ectopic expression of LINC00526 inhibits glioma cell proliferation, migration, and invasion. LINC00526 silencing promotes glioma cell proliferation, migration and invasion. Mechanistically, we found that LINC00526 directly interacts with EZH2, represses the binding of EZH2 to AXL promoter, attenuates the transcriptional activating roles of EZH2 on AXL , and therefore represses AXL expression. Via repressing AXL, LINC00526 further represses PI3K/Akt/NF‐κB signalling. Intriguingly, we identified that NFKB1 and NFKB2 directly binds LINC00526 promoter and represses LINC00526 transcription. We further found that via activating NF‐κB signalling, AXL represses LINC00526 transcription. Therefore, LINC00526/EZH2/AXL/PI3K/Akt/NF‐κB form a feedback loop in glioma. Analysis of the TCGA data revealed that the expression of LINC00526 is inversely correlated with that of AXL in glioma tissues. In addition, functional rescue assays revealed that the tumour suppressive roles of LINC00526 are dependent on the negative regulation of AXL. Collectively, our data identified LINC00526 as a tumour suppressor in glioma via forming a double negative feedback loop with AXL. Our data also suggested LINC00526 as a potential prognostic biomarker and therapeutic candidate for glioma.

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Section: Discussionsupporting

confidence: 63%

Long non‐coding RNA LINC00526 represses glioma progression via forming a double negative feedback loop with AXL

Yan

et al. 2019

J Cellular Molecular Medi

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“…These effects have been linked to cancer progression and poor overall survival (157). In addition, convincing evidence shows that the efficiencies of these signaling pathways are positively or negatively modulated by miRNAs and lncRNAs (39)(40)(41)(42)(43)(44)(45)(46)(47)(48). These studies suggest that aberrant activation of multiple pathways can induce the cancer hallmarks, particularly hallmarks (1), (4), and (6), and can contribute to caner initiation and progression of glioma.…”

Section: Major Signaling Pathways Regulated By Mirnas and Lncrnas Invmentioning

confidence: 99%

“…In the ERK/MAPK signaling pathway, the lncRNAs, GAS5, HOTAIR and CRNDE modulate the signaling efficiency by targeting miR-18a-5p, miR-326, and miR-186, respectively, which contribute to the activation of invasion and metastasis of glioma cells (39,41,45) (Figure 11). miR-18a-5p functions as an oncogenic miRNA by reducing the levels of Neogenin mRNA by destabilization (170).…”

Section: Mirnas and Lncrnas That Modulate The Activation Of Invasion mentioning

confidence: 99%

“…Neogenin is a Netrin-1 receptor that represses ERK/MAPK signaling, which leads to reduced migration and invasion of glioma cells (170). Indeed, miR-18a-5p de-repressed the Neogenin-dependent reduction of migration and invasion of glioma cells (45). The lncRNA, GAS5, was identified as a spliced form of an lncRNA in which introns encode small nucleolar RNAs (snoRNAs) (171).…”

Section: Mirnas and Lncrnas That Modulate The Activation Of Invasion mentioning

confidence: 99%

“…Moreover, a few lncRNAs have the potential to affect protein stability (37,38), although interactions between lncRNAs and proteins have not been fully investigated. lncRNAs in gliomagenesis can act as ceRNAs that counteract miRNAs to modulate the expression levels of target mRNAs (39)(40)(41)(42)(43)(44)(45)(46)(47)(48). Of note, it has been argued that the stoichiometric relationship between miRNAs and ceRNAs is crucial in the inhibition of miRNAs by ceRNAs (17,49).…”

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confidence: 99%

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Regulatory non-coding RNAs in nervous system development and disease

Kimura

Yamada

2019

Front Biosci

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Introduction 3. Regulation of nervous system development by long non-coding RNAs 3.1. LncRNAs are involved in neural differentiation 3.2. LncRNAs are involved in synaptogenesis and synaptic plasticity 4. Functional involvement of long non-coding RNAs in neurological diseases 4.1. Alzheimer's disease (AD) 4.2. Parkinson's disease (PD) 4.2.1. Malat1 inhibits alpha-synuclein protein degradation and antagonizes miR-124 4.2.2. HOTAIR enhances both LRRK2 mRNA stability and caspase-3 activity 4.2.3. MAPT-AS1 reduces MAPT expression in an epigenetic manner 4.2.4. Roles of PINK1, Parkin, and NEAT1 in neuronal degeneration via disruption of mitochondrial homeostasis 4.3. Glioma 4.3.1. Major signaling pathways regulated by miRNAs and lncRNAs for glioma initiation and progression 4.3.2. Roles of signaling pathways related to cancer hallmarks 4.3.3. miRNAs and lncRNAs that modulate sustained proliferative signaling 4.3.4. miRNAs and lncRNAs that modulate the activation of invasion and metastasis 4.3.5. miRNAs and lncRNAs that modulate resistance to cell death 4.3.6. Possible mechanisms for dysregulation of lncRNA expression in glioma development 5. Perspectives 6. Acknowledgements 7. References

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Long noncoding RNA‐GAS5 attenuates progression of glioma by eliminating microRNA‐10b and Sirtuin 1 in U251 and A172 cells

et al. 2019

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Long noncoding RNA (lncRNA) growth arrest‐specific 5 (GAS5) is implicated in several cancers via modulating microRNAs (miRs). However, little information is available about the correlation between GAS5 and miR‐10b. Therefore, we sought out to investigate the biological role of GAS5‐miR‐10b node mainly in glioma cells. We artificially modulated GAS5 to explore its roles in viability assayed by cell counting kit‐8 (CCK‐8), motile activities by 24‐Transwell assay, as well as apoptosis by a flow cytometer and Western blot assay. miR‐10b and Sirtuin 1 (Sirt1) were quantified by qRT‐PCR. After co‐transfection, we analyzed the viability, migration, invasion, apoptosis, and Sirt1 expression. Western blot was implemented to detect the phosphorylated forms of PTEN, PI3K, AKT, MEK, and ERK. GAS5 inhibited proliferation and motile behaviors, and fortified apoptosis. As for the viability and motile activities, the property of GAS5 was reversed in miR‐10b‐replenished U251 and A172 cells, while maintained in miR‐10b‐deficient cells. Additionally, GAS5‐induced apoptosis was abolished by miR‐10b overexpression while fortified by miR‐10b silence. Besides, GAS5 negatively modulated Sirt1 via miR‐10b. Moreover, Sirt1 negatively modulated PTEN and positively mediated the abovementioned regulators. GAS5 represses the process of glioma cells by decreasing miR‐10b, which as accompanied by Sirt1 silence‐induced inactivation of PTEN/PI3K/AKT and MEK/ERK cascades.

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Long noncoding RNA GAS5 regulates the proliferation, migration, and invasion of glioma cells by negatively regulating miR‐18a‐5p

Abstract: Taken together, our findings suggest that GAS5 is a tumor suppressor in human gliomas that acts in part by repressing miR-18a-5p.

Cited by 67 publications

References 50 publications

Long non‐coding RNA LINC00526 represses glioma progression via forming a double negative feedback loop with AXL

Long non‐coding RNA LINC00526 represses glioma progression via forming a double negative feedback loop with AXL

Regulatory non-coding RNAs in nervous system development and disease

Long noncoding RNA‐GAS5 attenuates progression of glioma by eliminating microRNA‐10b and Sirtuin 1 in U251 and A172 cells

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