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

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.

[1]  Xidi Wang,et al.  Oncogenic lncRNA ZNF561-AS1 is essential for colorectal cancer proliferation and survival through regulation of miR-26a-3p/miR-128-5p-SRSF6 axis , 2021, Journal of experimental & clinical cancer research : CR.

[2]  Maode Wang,et al.  BRAF AMP Frequently Co-occurs With IDH1/2, TP53, and ATRX Mutations in Adult Patients With Gliomas and Is Associated With Poorer Survival Than That of Patients Harboring BRAF V600E , 2021, Frontiers in Oncology.

[3]  A. Shilatifard,et al.  Effects of H3.3G34V mutation on genomic H3K36 and H3K27 methylation patterns in isogenic pediatric glioma cells , 2020, Acta neuropathologica communications.

[4]  W. Zeng,et al.  NF-κB-mediated lncRNA AC007271.3 promotes carcinogenesis of oral squamous cell carcinoma by regulating miR-125b-2-3p/Slug , 2020, Cell Death & Disease.

[5]  Mingchen Xiong,et al.  Epigenetic modification mechanisms involved in keloid: current status and prospect , 2020, Clinical epigenetics.

[6]  Zuolong Wu,et al.  A four-methylated LncRNA signature predicts survival of osteosarcoma patients based on machine learning. , 2020, Genomics.

[7]  Shuhua Zheng,et al.  Identification of a cullin5-RING E3 ligase transcriptome signature in glioblastoma multiforme , 2020, Aging.

[8]  Jian Zheng,et al.  Interaction of BACH2 with FUS promotes malignant progression of glioma cells via the TSLNC8–miR‐10b‐5p–WWC3 pathway , 2020, Molecular oncology.

[9]  F. Thorsen,et al.  Glioblastoma Therapy Using Codelivery of Cisplatin and Glutathione Peroxidase Targeting siRNA from Iron Oxide Nanoparticles. , 2020, ACS applied materials & interfaces.

[10]  K. Zhao,et al.  Prognostic significance of ARL9 and its methylation in low-grade glioma , 2020, Genomics.

[11]  Jiali Yang,et al.  Methylation-mediated LINC00261 suppresses pancreatic cancer progression by epigenetically inhibiting c-Myc transcription , 2020, Theranostics.

[12]  Wei Zhao,et al.  LncRNA KTN1-AS1 promotes the progression of non-small cell lung cancer via sponging of miR-130a-5p and activation of PDPK1 , 2020, Oncogene.

[13]  Ling-Ling Chen,et al.  Mechanisms of Long Noncoding RNA Nuclear Retention. , 2020, Trends in biochemical sciences.

[14]  A. Barciszewska,et al.  DNA methylation analysis with methylation‐sensitive high‐resolution melting (MS‐HRM) reveals gene panel for glioma characteristics , 2020, CNS neuroscience & therapeutics.

[15]  Fulin Xu,et al.  Long noncoding RNA HNF1A‐AS1 regulates proliferation and apoptosis of glioma through activation of the JNK signaling pathway via miR‐363‐3p/MAP2K4 , 2020, Journal of cellular physiology.

[16]  Marilyn M. Li,et al.  Congenital tumors of the central nervous system: an institutional review of 64 cases with emphasis on tumors with unique histologic and molecular characteristics , 2020, Brain pathology.

[17]  C. Scapoli,et al.  A Molecular Signature associated with prolonged survival in Glioblastoma patients treated with Regorafenib. , 2020, Neuro-oncology.

[18]  I. Nookaew,et al.  A novel Cas9-targeted long-read assay for simultaneous detection of IDH1/2 mutations and clinically relevant MGMT methylation in fresh biopsies of diffuse glioma , 2020, Acta Neuropathologica Communications.

[19]  Dapeng Liang,et al.  MOB2 suppresses GBM cell migration and invasion via regulation of FAK/Akt and cAMP/PKA signaling , 2020, Cell Death & Disease.

[20]  Yong Peng,et al.  Exosomal noncoding RNAs in Glioma: biological functions and potential clinical applications , 2020, Molecular Cancer.

[21]  Juxiang Chen,et al.  An eight-mRNA signature outperforms the lncRNA-based signature in predicting prognosis of patients with glioblastoma , 2020, BMC Medical Genetics.

[22]  Er-Bao Bian,et al.  Super-enhancers: A new frontier for glioma treatment. , 2020, Biochimica et biophysica acta. Reviews on cancer.

[23]  Y. You,et al.  DNA-methylation-mediated activating of lncRNA SNHG12 promotes temozolomide resistance in glioblastoma , 2020, Molecular Cancer.

[24]  Zi-heng Wu,et al.  lncRNA KCNQ1OT1 Suppresses the Inflammation and Proliferation of Vascular Smooth Muscle Cells through IκBa in Intimal Hyperplasia , 2020, Molecular therapy. Nucleic acids.

[25]  P. Walczak,et al.  Modeling human pediatric and adult gliomas in immunocompetent mice through costimulatory blockade , 2020, Oncoimmunology.

[26]  Hong Wang,et al.  Long noncoding RNA HAS2‐AS1 promotes tumor progression in glioblastoma via functioning as a competing endogenous RNA , 2020, Journal of cellular biochemistry.

[27]  Yuejin Wu,et al.  Specific glioblastoma multiforme prognostic-subtype distinctions based on DNA methylation patterns , 2019, Cancer Gene Therapy.

[28]  M. Taheri,et al.  Maternally expressed gene 3 (MEG3): A tumor suppressor long non coding RNA. , 2019, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[29]  R. Klose,et al.  Distinct contributions of DNA methylation and histone acetylation to the genomic occupancy of transcription factors , 2020, Genome research.

[30]  Ya-Zhou Sun,et al.  RNA methylation and diseases: experimental results, databases, Web servers and computational models , 2019, Briefings Bioinform..

[31]  B. Lu,et al.  NLRP3 Promotes Glioma Cell Proliferation and Invasion via the Interleukin-1β/NF-κB p65 Signals. , 2019, Oncology research.

[32]  Longzhou Zhang,et al.  Knockdown of NEAT1 repressed the malignant progression of glioma through sponging miR‐107 and inhibiting CDK14 , 2018, Journal of cellular physiology.

[33]  T. Jiang,et al.  A novel analytical model of MGMT methylation pyrosequencing offers improved predictive performance in patients with gliomas , 2018, Modern Pathology.

[34]  Martin Sill,et al.  Practical implementation of DNA methylation and copy-number-based CNS tumor diagnostics: the Heidelberg experience , 2018, Acta Neuropathologica.

[35]  J. Mosser,et al.  A novel prognostic six‐CpG signature in glioblastomas , 2018, CNS neuroscience & therapeutics.

[36]  Minghua Wu,et al.  New insights into long noncoding RNAs and their roles in glioma , 2018, Molecular Cancer.

[37]  M. Gorospe,et al.  Long Noncoding RNA uc.173 Promotes Renewal of the Intestinal Mucosa by Inducing Degradation of MicroRNA 195. , 2017, Gastroenterology.

[38]  Nathan C. Sheffield,et al.  The DNA methylation landscape of glioblastoma disease progression shows extensive heterogeneity in time and space , 2017, bioRxiv.

[39]  Jia Wen Liang,et al.  Aberrant Methylation-Mediated Silencing of lncRNA MEG3 Functions as a ceRNA in Esophageal Cancer , 2017, Molecular Cancer Research.

[40]  Cheng Li,et al.  GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses , 2017, Nucleic Acids Res..

[41]  J. Krijgsveld,et al.  Proteome and Secretome Characterization of Glioblastoma‐Derived Neural Stem Cells , 2017, Stem cells.

[42]  B. Zhao,et al.  Long non-coding RNA ATB promotes glioma malignancy by negatively regulating miR-200a , 2016, Journal of experimental & clinical cancer research : CR.

[43]  B. Zhao,et al.  Epigenetic modification of miR-141 regulates SKA2 by an endogenous ‘sponge’ HOTAIR in glioma , 2016, Oncotarget.

[44]  B. Zhao,et al.  Epigenetic repression of long non-coding RNA MEG3 mediated by DNMT1 represses the p53 pathway in gliomas. , 2016, International journal of oncology.

[45]  G. Mills,et al.  Comprehensive Genomic Characterization of Long Non-coding RNAs across Human Cancers. , 2015, Cancer cell.

[46]  Hongzhe Li,et al.  A functional genomic approach identifies FAL1 as an oncogenic long noncoding RNA that associates with BMI1 and represses p21 expression in cancer. , 2014, Cancer cell.

[47]  D. Stupack,et al.  The Ras-related Protein, Rap1A, Mediates Thrombin-stimulated, Integrin-dependent Glioblastoma Cell Proliferation and Tumor Growth* , 2014, The Journal of Biological Chemistry.

[48]  C. Brennan,et al.  Perivascular nitric oxide activates notch signaling and promotes stem-like character in PDGF-induced glioma cells. , 2010, Cell stem cell.

[49]  O. Jäkel,et al.  THE HEIDELBERG EXPERIENCE , 2009 .

[50]  C. V. D. van de Velde,et al.  70-Gene Signature in Early-Stage Breast Cancer. , 2016, The New England journal of medicine.