RNA Editing in Glioma as a Sexually Dimorphic Prognostic Factor That Affects mRNA Abundance in Fatty Acid Metabolism and Inflammation Pathways

RNA editing alters the nucleotide sequence and has been associated with cancer progression. However, little is known about its prognostic and regulatory roles in glioma, one of the most common types of primary brain tumors. We characterized and analyzed RNA editomes of glioblastoma and isocitrate de...

Full description

Bibliographic Details
Main Authors: Sheng-Hau Lin, Sean Chun-Chang Chen
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/11/7/1231
_version_ 1797439849133768704
author Sheng-Hau Lin
Sean Chun-Chang Chen
author_facet Sheng-Hau Lin
Sean Chun-Chang Chen
author_sort Sheng-Hau Lin
collection DOAJ
description RNA editing alters the nucleotide sequence and has been associated with cancer progression. However, little is known about its prognostic and regulatory roles in glioma, one of the most common types of primary brain tumors. We characterized and analyzed RNA editomes of glioblastoma and isocitrate dehydrogenase mutated (IDH-MUT) gliomas from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas (CGGA). We showed that editing change during glioma progression was another layer of molecular alterations and that editing profiles predicted the prognosis of glioblastoma and IDH-MUT gliomas in a sex-dependent manner. Hyper-editing was associated with poor survival in females but better survival in males. Moreover, noncoding editing events impacted mRNA abundance of the host genes. Genes associated with inflammatory response (e.g., <i>EIF2AK2</i>, a key mediator of innate immunity) and fatty acid oxidation (e.g., <i>acyl-CoA oxidase 1</i>, the rate-limiting enzyme in fatty acid β-oxidation) were editing-regulated and associated with glioma progression. The above findings were further validated in CGGA samples. Establishment of the prognostic and regulatory roles of RNA editing in glioma holds promise for developing editing-based therapeutic strategies against glioma progression. Furthermore, sexual dimorphism at the epitranscriptional level highlights the importance of developing sex-specific treatments for glioma.
first_indexed 2024-03-09T11:59:40Z
format Article
id doaj.art-7fb7996a7d594fcea1cffa3716156a29
institution Directory Open Access Journal
issn 2073-4409
language English
last_indexed 2024-03-09T11:59:40Z
publishDate 2022-04-01
publisher MDPI AG
record_format Article
series Cells
spelling doaj.art-7fb7996a7d594fcea1cffa3716156a292023-11-30T23:05:18ZengMDPI AGCells2073-44092022-04-01117123110.3390/cells11071231RNA Editing in Glioma as a Sexually Dimorphic Prognostic Factor That Affects mRNA Abundance in Fatty Acid Metabolism and Inflammation PathwaysSheng-Hau Lin0Sean Chun-Chang Chen1Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, TaiwanGraduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, TaiwanRNA editing alters the nucleotide sequence and has been associated with cancer progression. However, little is known about its prognostic and regulatory roles in glioma, one of the most common types of primary brain tumors. We characterized and analyzed RNA editomes of glioblastoma and isocitrate dehydrogenase mutated (IDH-MUT) gliomas from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas (CGGA). We showed that editing change during glioma progression was another layer of molecular alterations and that editing profiles predicted the prognosis of glioblastoma and IDH-MUT gliomas in a sex-dependent manner. Hyper-editing was associated with poor survival in females but better survival in males. Moreover, noncoding editing events impacted mRNA abundance of the host genes. Genes associated with inflammatory response (e.g., <i>EIF2AK2</i>, a key mediator of innate immunity) and fatty acid oxidation (e.g., <i>acyl-CoA oxidase 1</i>, the rate-limiting enzyme in fatty acid β-oxidation) were editing-regulated and associated with glioma progression. The above findings were further validated in CGGA samples. Establishment of the prognostic and regulatory roles of RNA editing in glioma holds promise for developing editing-based therapeutic strategies against glioma progression. Furthermore, sexual dimorphism at the epitranscriptional level highlights the importance of developing sex-specific treatments for glioma.https://www.mdpi.com/2073-4409/11/7/1231RNA editingglioblastomasurvivalmachine learningsexual dimorphismADAR
spellingShingle Sheng-Hau Lin
Sean Chun-Chang Chen
RNA Editing in Glioma as a Sexually Dimorphic Prognostic Factor That Affects mRNA Abundance in Fatty Acid Metabolism and Inflammation Pathways
Cells
RNA editing
glioblastoma
survival
machine learning
sexual dimorphism
ADAR
title RNA Editing in Glioma as a Sexually Dimorphic Prognostic Factor That Affects mRNA Abundance in Fatty Acid Metabolism and Inflammation Pathways
title_full RNA Editing in Glioma as a Sexually Dimorphic Prognostic Factor That Affects mRNA Abundance in Fatty Acid Metabolism and Inflammation Pathways
title_fullStr RNA Editing in Glioma as a Sexually Dimorphic Prognostic Factor That Affects mRNA Abundance in Fatty Acid Metabolism and Inflammation Pathways
title_full_unstemmed RNA Editing in Glioma as a Sexually Dimorphic Prognostic Factor That Affects mRNA Abundance in Fatty Acid Metabolism and Inflammation Pathways
title_short RNA Editing in Glioma as a Sexually Dimorphic Prognostic Factor That Affects mRNA Abundance in Fatty Acid Metabolism and Inflammation Pathways
title_sort rna editing in glioma as a sexually dimorphic prognostic factor that affects mrna abundance in fatty acid metabolism and inflammation pathways
topic RNA editing
glioblastoma
survival
machine learning
sexual dimorphism
ADAR
url https://www.mdpi.com/2073-4409/11/7/1231
work_keys_str_mv AT shenghaulin rnaeditingingliomaasasexuallydimorphicprognosticfactorthataffectsmrnaabundanceinfattyacidmetabolismandinflammationpathways
AT seanchunchangchen rnaeditingingliomaasasexuallydimorphicprognosticfactorthataffectsmrnaabundanceinfattyacidmetabolismandinflammationpathways