Dataset Information

Long Noncoding Ribonucleic Acid SNHG18 Promotes Glioma Cell Motility via Disruption of ?-Enolase Nucleocytoplasmic Transport.

ABSTRACT: Glioma is a common malignancy with poor prognosis. Recent evidence suggests that the pathogenesis and progression of glioma involve long noncoding RNAs (lncRNAs). Previously, we showed that glioma cell radioresistance was enhanced by lncRNA SNHG18 in vitro and in vivo. In the present study, we showed that SNHG18 promoted the invasion and migration of glioma cells. SNHG18 was demonstrated to regulate the progression of epithelial-mesenchymal transition and cytoskeleton remodeling, thereby affecting cell motility. Furthermore, the promotion of invasion evoked by SNHG18 overexpression could be rescued by ?-enolase (ENO1) deletion. Moreover, rather than altering ENO1 expression, SNHG18 suppressed its nucleocytoplasmic transport by directly combining with ENO1 in glioma cells. The results suggested that SNHG18 inhibited the nucleocytoplasmic transport of ENO1 to promote cell motility. The results reveal the mechanism by which this lncRNA affects tumorigenesis and metastasis, forming the basis for further research that will lead to novel strategies to treat glioma.

SUBMITTER: Zheng R

PROVIDER: S-EPMC6865306 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Long Noncoding Ribonucleic Acid SNHG18 Promotes Glioma Cell Motility via Disruption of α-Enolase Nucleocytoplasmic Transport.

Zheng Rong R Yao Qiwei Q Li XiaoBo X Xu Benhua B

Frontiers in genetics 20191113

Glioma is a common malignancy with poor prognosis. Recent evidence suggests that the pathogenesis and progression of glioma involve long noncoding RNAs (lncRNAs). Previously, we showed that glioma cell radioresistance was enhanced by lncRNA SNHG18 in vitro and in vivo. In the present study, we showed that SNHG18 promoted the invasion and migration of glioma cells. SNHG18 was demonstrated to regulate the progression of epithelial-mesenchymal transition and cytoskeleton ...[more]

PMID: 31798634

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Project description:BackgroundNuclear translocation of several oncogenic proteins have previously been reported, but neither the translocation of doublecortin (DCX) nor the mechanism involved has been studied. DCX is a neuronal microtubule-associated protein (MAP) that is crucial for adult neurogenesis and neuronal migration and has been associated with poor prognosis in gliomas.MethodsWe probed DCX expression in different grades of glioma tissues and conventional cells via western blotting. Then we analyzed the expression pattern in the Oncomine cancer profiling database. Confocal Immunofluorescence was used to detect DCX expression in the cellular compartments, while subcellular fractionation was probed via western blotting. Pulse shape height analysis was utilized to verify DCX localization in a larger population of cells. Co-immunoprecipitation was used in detecting DCX-import receptors interactions. To probe for DCX functions, stable cells expressing high DCX expression or knockdown were generated using CRISPR-Cas9 viral transfection, while plasmid site-directed mutant constructs were used to validate putative nuclear localization sequence (NLS) predicted via conventional algorithms and comparison with classical NLSs. in-silico modeling was performed to validate DCX interactions with import receptors via the selected putative NLS. Effects of DCX high expression, knockdown, mutation, and/or deletion of putative NLS sites were probed via Boyden's invasion assay and wound healing migration assays, and viability was detected by CCK8 assays in-vitro, while xenograft tumor model was performed in nude mice.ResultsDCX undergoes nucleocytoplasmic movement via the RanGTPase signaling pathway with an NLS located on the N-terminus between serine47-tyrosine70. This translocation could be stimulated by MARK's phosphorylation of the serine 47 residue flanking the NLS due to aberrant expression of glial cell line-derived neurotrophic factor (GDNF). High expression and nuclear accumulation of DCX improve invasive glioma abilities in-vitro and in-vivo. Moreover, knocking down or blocking DCX nuclear import attenuates invasiveness and proliferation of glioma cells.ConclusionCollectively, this study highlights a remarkable phenomenon in glioma, hence revealing potential glioma dependencies on DCX expression, which is amenable to targeted therapy. Video abstract.

Project description:BackgroundDue to their inherent role in cell function, long non-coding ribonucleic acids (lncRNAs) mediate changes in the microenvironment, and thereby participate in the development of cellular senescence.AimsThis study aimed to identify cellular senescence-related lncRNAs that could predict the prognosis of liver cancer.Methods and resultsGene expression and clinical data were downloaded from the UCSC Xena platform, ICGC, and TCGA databases. Cox regression and LASSO regression were used to establish a cellular senescence-related lncRNA model. ROC curves and Kaplan-Meier survival curves were then constructed to predict patient prognosis. Cox regression analysis and clinical characteristics were used to evaluate the capability of the model. Tumor mutational burden and tumor-infiltrating immune cell analyses were subsequently performed in the risk subgroups and the samples in the entire cohort were reclustered. Finally, potential small molecule immune-targeted drugs were identified based on the model. The cellular senescence-related prognostic model that was constructed based on AGAP11 and FAM182B. Along with the results of Cox regression and Lasso regression, the risk score was found to be an independent factor for predicting overall survival in cohorts. In the subgroup analysis, the prognosis of the low-risk group in each cohort was significantly higher than that of the high-risk group; the area under temporal ROC curves and clinical ROC curves were all greater than 0.65, respectively. C-index shows that the risk scores are greater than 0.6, showing the stability of the model. The high-risk group demonstrated lower tumor microenvironment and higher tumor mutational burden scores, further verifying the reliability of the model grouping results. Analysis of tumor-infiltrating immune cells indicated that CD8+ and γδ T cells were more abundant among patients in the low-risk group; cluster reorganization indicated that the two groups had different prognoses and proportions of immune cells. The p value of potential drugs predicted based on the expression of model lncRNAs were all less than .05, demonstrating the potential of model lncRNAs as therapeutic targets to some extent.ConclusionA prognostic model based on cellular senescence-associated lncRNAs was established and this may be used as a potential biomarker for the prognosis assessment of liver cancer patients.

Project description:PurposeThe overall biological roles and clinical significance of most long noncoding RNAs (lncRNA) in chemosensitivity are not fully understood. We investigated the biological function, mechanism, and clinical significance of lncRNA NR_034085, which we termed miRNA processing-related lncRNA (MPRL), in tongue squamous cell carcinoma (TSCC).Experimental designLncRNA expression in TSCC cell lines with cisplatin treatment was measured by lncRNA microarray and confirmed in TSCC tissues. The functional roles of MPRL were demonstrated by a series of in vitro and in vivo experiments. The miRNA profiles, RNA pull-down, RNA immunoprecipitation, serial deletion analysis, and luciferase analyses were used to investigate the potential mechanisms of MPRL.ResultsWe found that MPRL expression was significantly upregulated in TSCC cell lines treated with cisplatin and transactivated by E2F1. MPRL controlled mitochondrial fission and cisplatin sensitivity through miR-483-5p. In exploring the underlying interaction between MPRL and miR-483-5p, we identified that cytoplasmic MPRL directly binds to pre-miR-483 within the loop region and blocks pre-miR-483 recognition and cleavage by TRBP-DICER-complex, thereby inhibiting miR-483-5p generation and upregulating miR-483-5p downstream target-FIS1 expression. Furthermore, overexpression or knockdown MPRL altered tumor apoptosis and growth in mouse xenografts. Importantly, we found that high expression of MPRL and pre-miR-483, and low expression of miR-483-5p were significantly associated with neoadjuvant chemosensitivity and better TSCC patients' prognosis.ConclusionsWe propose a model in which lncRNAs impair microprocessor recognition and are efficient of pre-miRNA cropping. In addition, our study reveals a novel regulatory network for mitochondrial fission and chemosensitivity and new biomarkers for prediction of neoadjuvant chemosensitivity in TSCC.These findings uncover a novel mechanism by which lncRNA determines mitochondrial fission and cisplatin chemosensitivity by inhibition of pre-miRNA processing and provide for the first time the rationale for lncRNA and miRNA biogenesis for predicting chemosensitivity and patient clinical prognosis.

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Long Noncoding Ribonucleic Acid SNHG18 Promotes Glioma Cell Motility via Disruption of ?-Enolase Nucleocytoplasmic Transport.

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Long Noncoding Ribonucleic Acid <i>SNHG18</i> Promotes Glioma Cell Motility <i>via</i> Disruption of α-Enolase Nucleocytoplasmic Transport.

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