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      LncRNAs associated with glioblastoma: From transcriptional noise to novel regulators with a promising role in therapeutics

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          Abstract

          Glioblastoma multiforme (GBM) is the most widespread and aggressive subtype of glioma in adult patients. Numerous long non-coding RNAs (lncRNAs) are deregulated or differentially expressed in GBM. These lncRNAs possess unique regulatory functions in GBM cells, ranging from high invasion/migration to recurrence. This review outlines the present status of specific involvement of lncRNAs in GBM pathogenesis, with a focus on their association with key molecular and cellular regulatory mechanisms. Also, we highlighted the potential of different novel RNA-based strategies that may be beneficial for therapeutic purposes.

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          Abstract

          GBM is invasive and accounts for 80% of all primary brain tumors. Most lncRNAs in glioma are aberrantly expressed and participate in the regulation of cellular processes and chemoresistance. Approaches such as RNAi, CRISPR-Cas9, NATs, and ASOs are used to target lncRNAs for their use in therapeutics

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          The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary.

          David N Louis, Arie Perry, Guido Reifenberger … (2016)
          The 2016 World Health Organization Classification of Tumors of the Central Nervous System is both a conceptual and practical advance over its 2007 predecessor. For the first time, the WHO classification of CNS tumors uses molecular parameters in addition to histology to define many tumor entities, thus formulating a concept for how CNS tumor diagnoses should be structured in the molecular era. As such, the 2016 CNS WHO presents major restructuring of the diffuse gliomas, medulloblastomas and other embryonal tumors, and incorporates new entities that are defined by both histology and molecular features, including glioblastoma, IDH-wildtype and glioblastoma, IDH-mutant; diffuse midline glioma, H3 K27M-mutant; RELA fusion-positive ependymoma; medulloblastoma, WNT-activated and medulloblastoma, SHH-activated; and embryonal tumour with multilayered rosettes, C19MC-altered. The 2016 edition has added newly recognized neoplasms, and has deleted some entities, variants and patterns that no longer have diagnostic and/or biological relevance. Other notable changes include the addition of brain invasion as a criterion for atypical meningioma and the introduction of a soft tissue-type grading system for the now combined entity of solitary fibrous tumor / hemangiopericytoma-a departure from the manner by which other CNS tumors are graded. Overall, it is hoped that the 2016 CNS WHO will facilitate clinical, experimental and epidemiological studies that will lead to improvements in the lives of patients with brain tumors.
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            The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression

            Thomas Derrien, Rory Johnson, Giovanni Bussotti … (2012)
            The human genome contains many thousands of long noncoding RNAs (lncRNAs). While several studies have demonstrated compelling biological and disease roles for individual examples, analytical and experimental approaches to investigate these genes have been hampered by the lack of comprehensive lncRNA annotation. Here, we present and analyze the most complete human lncRNA annotation to date, produced by the GENCODE consortium within the framework of the ENCODE project and comprising 9277 manually annotated genes producing 14,880 transcripts. Our analyses indicate that lncRNAs are generated through pathways similar to that of protein-coding genes, with similar histone-modification profiles, splicing signals, and exon/intron lengths. In contrast to protein-coding genes, however, lncRNAs display a striking bias toward two-exon transcripts, they are predominantly localized in the chromatin and nucleus, and a fraction appear to be preferentially processed into small RNAs. They are under stronger selective pressure than neutrally evolving sequences—particularly in their promoter regions, which display levels of selection comparable to protein-coding genes. Importantly, about one-third seem to have arisen within the primate lineage. Comprehensive analysis of their expression in multiple human organs and brain regions shows that lncRNAs are generally lower expressed than protein-coding genes, and display more tissue-specific expression patterns, with a large fraction of tissue-specific lncRNAs expressed in the brain. Expression correlation analysis indicates that lncRNAs show particularly striking positive correlation with the expression of antisense coding genes. This GENCODE annotation represents a valuable resource for future studies of lncRNAs.
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              DNA methylation-based classification of central nervous system tumours

              David Capper, David Jones, Martin Sill … (2018)
              Summary Accurate pathological diagnosis is crucial for optimal management of cancer patients. For the ~100 known central nervous system (CNS) tumour entities, standardization of the diagnostic process has been shown to be particularly challenging - with substantial inter-observer variability in the histopathological diagnosis of many tumour types. We herein present the development of a comprehensive approach for DNA methylation-based CNS tumour classification across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that availability of this method may have substantial impact on diagnostic precision compared with standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility we have designed a free online classifier tool (www.molecularneuropathology.org) requiring no additional onsite data processing. Our results provide a blueprint for the generation of machine learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.
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                Author and article information

                Contributors
                Amit Kumar Pandey
                Journal
                Journal ID (nlm-ta): Mol Ther Nucleic Acids
                Journal ID (iso-abbrev): Mol Ther Nucleic Acids
                Title: Molecular Therapy. Nucleic Acids
                Publisher: American Society of Gene & Cell Therapy
                ISSN (Electronic): 2162-2531
                Publication date PMC-release: 02 April 2021
                Publication date Collection: 04 June 2021
                Publication date (Electronic): 02 April 2021
                Volume: 24
                Pages: 728-742
                Affiliations
                [1 ]Amity Institute of Biotechnology, Amity University Haryana, Panchgaon, Manesar, Haryana 122413, India
                [2 ]Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, GSP-7, Ulitsa Miklukho-Maklaya, 16/10, 117997 Moscow, Russian Federation
                [3 ]Faculty of Biology and Biotechnology, National Research University Higher School of Economics, Vavilova Street 7, 117312 Moscow, Russian Federation
                [4 ]La Canada High School, La Canada Flintridge, CA 91011, USA
                [5 ]Amity Institute of Molecular Medicine and Stem Cell Research (AIMMSCR), Amity University, Uttar Pradesh, Sector 125, Noida 201313, India
                Author notes
                [∗ ]Corresponding author: Amit Kumar Pandey, Amity Institute of Biotechnology, Amity University Haryana, Panchgaon, Manesar, Haryana 122413, India. akpandey1@ 123456ggn.amity.edu
                [6]

                These authors contributed equally

                Article
                Publisher Item ID: S2162-2531(21)00089-5
                DOI: 10.1016/j.omtn.2021.03.018
                PMC ID: 8099481
                PubMed ID: 33996255
                SO-VID: 372afdc2-e742-4f22-b217-bd7a7f4b6232
                Copyright © © 2021 The Author(s)
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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                Subject: Review

                ScienceOpen disciplines: Molecular medicine
                Keywords: long non-coding rnas,glioblastoma,blood-brain barrier,chemoresistance,therapeutics
                Data availability:
                ScienceOpen disciplines: Molecular medicine
                Keywords: long non-coding rnas, glioblastoma, blood-brain barrier, chemoresistance, therapeutics

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