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      A Signature of Nine lncRNA Methylated Genes Predicts Survival in Patients With Glioma

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          Abstract

          Glioma is one of the most common malignant tumors of the central nervous system, and its prognosis is extremely poor. Aberrant methylation of lncRNA promoter region is significantly associated with the prognosis of glioma patients. In this study, we investigated the potential impact of methylation of lncRNA promoter region in glioma patients to establish a signature of nine lncRNA methylated genes for determining glioma patient prognosis. Methylation data and clinical follow-up data were obtained from The Cancer Genome Atlas (TCGA). The multistep screening strategy identified nine lncRNA methylated genes that were significantly associated with the overall survival (OS) of glioma patients. Subsequently, we constructed a risk signature that containing nine lncRNA methylated genes. The risk signature successfully divided the glioma patients into high-risk and low-risk groups. Compared with the low-risk group, the high-risk group had a worse prognosis, higher glioma grade, and older age. Furthermore, we identified two lncRNAs termed PCBP1-AS1 and LINC02875 that may be involved in the malignant progression of glioma cells by using the TCGA database. Loss-of-function assays confirmed that knockdown of PCBP1-AS1 and LINC02875 inhibited the proliferation, migration, and invasion of glioma cells. Therefore, the nine lncRNA methylated genes signature may provide a novel predictor and therapeutic target for glioma patients.

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          GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses

          Abstract Tremendous amount of RNA sequencing data have been produced by large consortium projects such as TCGA and GTEx, creating new opportunities for data mining and deeper understanding of gene functions. While certain existing web servers are valuable and widely used, many expression analysis functions needed by experimental biologists are still not adequately addressed by these tools. We introduce GEPIA (Gene Expression Profiling Interactive Analysis), a web-based tool to deliver fast and customizable functionalities based on TCGA and GTEx data. GEPIA provides key interactive and customizable functions including differential expression analysis, profiling plotting, correlation analysis, patient survival analysis, similar gene detection and dimensionality reduction analysis. The comprehensive expression analyses with simple clicking through GEPIA greatly facilitate data mining in wide research areas, scientific discussion and the therapeutic discovery process. GEPIA fills in the gap between cancer genomics big data and the delivery of integrated information to end users, thus helping unleash the value of the current data resources. GEPIA is available at http://gepia.cancer-pku.cn/.
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            New insights into long noncoding RNAs and their roles in glioma

            Glioma is one of the most prevalent types of primary intracranial carcinoma with varying malignancy grades I–IV and histological subtypes, including astrocytomas, glioblastoma multiform (GBM), oligodendrogliomas and mixed tumors. Glioma is characterized by rapid cell proliferation and angiogenesis, and the WHO grade IV glioblastoma, which is highly malignant with poor prognosis because GBM stem-like cells (GSCs) are resistant to conventional therapy and easily recrudescent, accounts for the majority of gliomas. Consequently, investigations exploring the accurate molecular mechanisms and reliable therapeutic targets for gliomas have drawn extensive attention. Based on the increasing amount of functional lncRNAs aberrantly expressed in glioma tissues and cell lines, lncRNAs might be critical for glioma initiation, progression and other malignant phenotypes. This review summarizes the latest insights into the lncRNA field and their functional roles in glioma, therefore evaluating the potential clinical applications of lncRNAs as prospective novel biomarkers and therapeutic targets.
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              Perivascular nitric oxide activates notch signaling and promotes stem-like character in PDGF-induced glioma cells.

              eNOS expression is elevated in human glioblastomas and correlated with increased tumor growth and aggressive character. We investigated the potential role of nitric oxide (NO) activity in the perivascular niche (PVN) using a genetic engineered mouse model of PDGF-induced gliomas. eNOS expression is highly elevated in tumor vascular endothelium adjacent to perivascular glioma cells expressing Nestin, Notch, and the NO receptor, sGC. In addition, the NO/cGMP/PKG pathway drives Notch signaling in PDGF-induced gliomas in vitro, and induces the side population phenotype in primary glioma cell cultures. NO also increases neurosphere forming capacity of PDGF-driven glioma primary cultures, and enhances their tumorigenic capacity in vivo. Loss of NO activity in these tumors suppresses Notch signaling in vivo and prolongs survival of mice. This mechanism is conserved in human PDGFR amplified gliomas. The NO/cGMP/PKG pathway's promotion of stem cell-like character in the tumor PVN may identify therapeutic targets for this subset of gliomas. Copyright 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                22 March 2021
                2021
                : 11
                : 646409
                Affiliations
                [1] 1Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University , Hefei, China
                [2] 2Cerebral Vascular Disease Research Center, Anhui Medical University , Hefei, China
                Author notes

                Edited by: Herui Wang, National Cancer Institute (NCI), United States

                Reviewed by: Ramon Garcia-Escudero, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, Spain; Qiuyan Guo, China Academy of Chinese Medical Sciences, China

                *Correspondence: Erbao Bian aydbeb@ 123456126.com

                This article was submitted to Neuro-Oncology and Neurosurgical Oncology, a section of the journal Frontiers in Oncology

                †These authors have contributed equally to this work and share first authorship

                Article
                10.3389/fonc.2021.646409
                8019920
                33828990
                d23d52b7-7d61-439c-9b72-96211fc24bb4
                Copyright © 2021 Cheng, Sun, Huang, Yue, Chen, Zhang, Zhao and Bian.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 26 December 2020
                : 24 February 2021
                Page count
                Figures: 9, Tables: 0, Equations: 0, References: 49, Pages: 14, Words: 8068
                Funding
                Funded by: National Natural Science Foundation of China-Guangdong Joint Fund 10.13039/501100014857
                Funded by: Anhui Provincial Key Research and Development Plan 10.13039/501100017668
                Categories
                Oncology
                Original Research

                Oncology & Radiotherapy
                glioma,long non-coding rna,methylation,epigenetics,prognosis
                Oncology & Radiotherapy
                glioma, long non-coding rna, methylation, epigenetics, prognosis

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