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pmid:34001135
Mir-139-5p inhibits glioma cell proliferation and progression by targeting GABRA1.
Lei Wang · Yan Liu · Zhengtao Yu · Jianwu Gong · Zhiyong Deng · Nianjun Ren · Zhe Zhong · Hao Cai · Zhi Tang · Haofeng Cheng · Shuai Chen · Zhengwen He
Journal of translational medicine · 2021 doi:10.1186/s12967-021-02880-9
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Complete file
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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.", "claims": [{"id": "claim-method", "statement": "Comparisons between the quantitative data were made using Student’s t test, with p < 0.05 considered statistically significant.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34001135", "locator": "sections[15] \"Statistical analysis\" paragraph 2", "quote": "Comparisons between the quantitative data were made using Student’s t test, with p < 0.05 considered statistically significant."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used or analyzed during the current study are available from The Chinese Glioma Genome Atlas (http://www.cgga.org.cn/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34001135", "locator": "sections[33] \"Availability of data and materials\" paragraph 2", "quote": "The datasets used or analyzed during the current study are available from The Chinese Glioma Genome Atlas (http://www.cgga.org.cn/)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:34001135"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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"4.634117944"], ["hsa-miR-137", "GABRA1", "Target", "− 2.997290651", "2.537054605"], ["hsa-miR-137", "GRIN2A", "Target", "− 2.997290651", "3.050424617"], ["hsa-miR-137", "HLF", "Target", "− 2.997290651", "5.341249022"], ["hsa-miR-137", "NETO1", "Target", "− 2.997290651", "4.134785091"], ["hsa-miR-137", "NRXN1", "Target", "− 2.997290651", "5.784845966"], ["hsa-miR-137", "NRXN3", "Target", "− 2.997290651", "3.652567346"], ["hsa-miR-137", "PLCB1", "Target", "− 2.997290651", "5.750675061"], ["hsa-miR-137", "PTGFRN", "Target", "− 2.997290651", "5.222125013"], ["hsa-miR-137", "PTPN5", "Target", "− 2.997290651", "3.471111043"], ["hsa-miR-137", "RAPGEF5", "Target", "− 2.997290651", "4.030838556"], ["hsa-miR-137", "RCAN2", "Target", "− 2.997290651", "5.450737004"], ["hsa-miR-137", "RGS7BP", "Target", "− 2.997290651", "4.314153573"], ["hsa-miR-137", "ST18", "Target", "− 2.997290651", "3.050911173"], ["hsa-miR-137", "SYT1", "Target", "− 2.997290651", "4.165893064"], ["hsa-miR-137", "TNC", 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