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Mir-139-5p inhibits glioma cell proliferation and progression by targeting GABRA1

Glioma is an extremely aggressive malignant neoplasm of the central nervous system. MicroRNA (miRNA) are known to bind to specific target mRNA to regulate post-transcriptional gene expression and are, therefore, currently regarded as promising biomarkers for glioma diagnosis and prognosis. The aim o...

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Autores principales: Wang, Lei, Liu, Yan, Yu, Zhengtao, Gong, Jianwu, Deng, Zhiyong, Ren, Nianjun, Zhong, Zhe, Cai, Hao, Tang, Zhi, Cheng, Haofeng, Chen, Shuai, He, Zhengwen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130534/
https://www.ncbi.nlm.nih.gov/pubmed/34001135
http://dx.doi.org/10.1186/s12967-021-02880-9
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author Wang, Lei
Liu, Yan
Yu, Zhengtao
Gong, Jianwu
Deng, Zhiyong
Ren, Nianjun
Zhong, Zhe
Cai, Hao
Tang, Zhi
Cheng, Haofeng
Chen, Shuai
He, Zhengwen
author_facet Wang, Lei
Liu, Yan
Yu, Zhengtao
Gong, Jianwu
Deng, Zhiyong
Ren, Nianjun
Zhong, Zhe
Cai, Hao
Tang, Zhi
Cheng, Haofeng
Chen, Shuai
He, Zhengwen
author_sort Wang, Lei
collection PubMed
description Glioma is an extremely aggressive malignant neoplasm of the central nervous system. MicroRNA (miRNA) are known to bind to specific target mRNA to regulate post-transcriptional gene expression and are, therefore, currently regarded as promising biomarkers for glioma diagnosis and prognosis. The aim of the present study was to examine the pathogenesis and potential molecular markers of glioma by comparing the differential expression of miRNA and mRNA between glioma tissue and peritumor brain tissue. We explored the impact of screened core miRNA and mRNA on cell proliferation, invasion, and migration of glioma. An miRNA expression profile dataset (GSE90603) and a transcriptome profile dataset (GSE90598) were downloaded from combined miRNA-mRNA microarray chips in the Gene Expression Omnibus (GEO) database. Overall, 59 differentially expressed miRNAs (DEMs) and 419 differentially expressed genes (DEGs) were identified using the R limma software package. FunRich software was used to predict DEM target genes and miRNA-gene pairs, and Perl software was used to find overlapping genes between DEGs and DEM target genes. There were 129 overlapping genes regulated by nine miRNAs between target genes of the DEMs and DEGs. The Chinese Glioma Genome Atlas(CGGA) was analyzed in order to identify miRNAs with diagnostic and prognostic significance. MiR-139-5p, miR-137, and miR-338-3p were validated to be significantly linked to prognosis in glioma patients. Finally, we validated that miR-139-5p affected glioma malignant biological behavior via targeting gamma-aminobutyric acid A receptor alpha 1(GABRA1) through rescue experiments. Low miR-139-5p expression was correlated with survival probability and World Health Organization (WHO) grade. MiR-139-5p overexpression inhibited cell proliferation, migration, and invasion of glioma in vitro. GABRA1 was identified as a functional downstream target of miR-139-5p. Decreased GABRA1 expression was related to similar biological roles as miR-139-5p overexpression while upregulation of GABRA1 effectively reversed the inhibition effects of miR-139-5p. These results demonstrate a novel axis for miR-139-5p/GABRA1 in glioma progression and provide potential prognostic predictors and therapeutic target for glioma patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-021-02880-9.
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spelling pubmed-81305342021-05-19 Mir-139-5p inhibits glioma cell proliferation and progression by targeting GABRA1 Wang, Lei Liu, Yan Yu, Zhengtao Gong, Jianwu Deng, Zhiyong Ren, Nianjun Zhong, Zhe Cai, Hao Tang, Zhi Cheng, Haofeng Chen, Shuai He, Zhengwen J Transl Med Research Glioma is an extremely aggressive malignant neoplasm of the central nervous system. MicroRNA (miRNA) are known to bind to specific target mRNA to regulate post-transcriptional gene expression and are, therefore, currently regarded as promising biomarkers for glioma diagnosis and prognosis. The aim of the present study was to examine the pathogenesis and potential molecular markers of glioma by comparing the differential expression of miRNA and mRNA between glioma tissue and peritumor brain tissue. We explored the impact of screened core miRNA and mRNA on cell proliferation, invasion, and migration of glioma. An miRNA expression profile dataset (GSE90603) and a transcriptome profile dataset (GSE90598) were downloaded from combined miRNA-mRNA microarray chips in the Gene Expression Omnibus (GEO) database. Overall, 59 differentially expressed miRNAs (DEMs) and 419 differentially expressed genes (DEGs) were identified using the R limma software package. FunRich software was used to predict DEM target genes and miRNA-gene pairs, and Perl software was used to find overlapping genes between DEGs and DEM target genes. There were 129 overlapping genes regulated by nine miRNAs between target genes of the DEMs and DEGs. The Chinese Glioma Genome Atlas(CGGA) was analyzed in order to identify miRNAs with diagnostic and prognostic significance. MiR-139-5p, miR-137, and miR-338-3p were validated to be significantly linked to prognosis in glioma patients. Finally, we validated that miR-139-5p affected glioma malignant biological behavior via targeting gamma-aminobutyric acid A receptor alpha 1(GABRA1) through rescue experiments. Low miR-139-5p expression was correlated with survival probability and World Health Organization (WHO) grade. MiR-139-5p overexpression inhibited cell proliferation, migration, and invasion of glioma in vitro. GABRA1 was identified as a functional downstream target of miR-139-5p. Decreased GABRA1 expression was related to similar biological roles as miR-139-5p overexpression while upregulation of GABRA1 effectively reversed the inhibition effects of miR-139-5p. These results demonstrate a novel axis for miR-139-5p/GABRA1 in glioma progression and provide potential prognostic predictors and therapeutic target for glioma patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-021-02880-9. BioMed Central 2021-05-17 /pmc/articles/PMC8130534/ /pubmed/34001135 http://dx.doi.org/10.1186/s12967-021-02880-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Wang, Lei
Liu, Yan
Yu, Zhengtao
Gong, Jianwu
Deng, Zhiyong
Ren, Nianjun
Zhong, Zhe
Cai, Hao
Tang, Zhi
Cheng, Haofeng
Chen, Shuai
He, Zhengwen
Mir-139-5p inhibits glioma cell proliferation and progression by targeting GABRA1
title Mir-139-5p inhibits glioma cell proliferation and progression by targeting GABRA1
title_full Mir-139-5p inhibits glioma cell proliferation and progression by targeting GABRA1
title_fullStr Mir-139-5p inhibits glioma cell proliferation and progression by targeting GABRA1
title_full_unstemmed Mir-139-5p inhibits glioma cell proliferation and progression by targeting GABRA1
title_short Mir-139-5p inhibits glioma cell proliferation and progression by targeting GABRA1
title_sort mir-139-5p inhibits glioma cell proliferation and progression by targeting gabra1
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130534/
https://www.ncbi.nlm.nih.gov/pubmed/34001135
http://dx.doi.org/10.1186/s12967-021-02880-9
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