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Decreased expression of SOX9 indicates a better prognosis and inhibits the growth of glioma cells by inducing cell cycle arrest.

ABSTRACT: Deregulation of SOX9 expression has been detected in various human cancer tissues; however, the functional role of SOX9 expression has not been fully elucidated in glioma. SOX9 expression in glioma tissues was analyzed using public tumor datasets and quantitative reverse transcription polymerase chain reaction. The association of SOX9 expression with clinical prognosis in glioma patients was analyzed by examining publically available microarray profiling datasets. The functional roles of SOX9 in glioma were examined using gene set enrichment analysis (GSEA). Cell growth was measured using soft agar colony formation assay, and the cell cycle was analyzed using flow cytometry. Our data showed that SOX9 expression was commonly upregulated in glioma tissues, and patients with high SOX9 levels had shorter survival times. GSEA identified that the gene sets regulating cell proliferation and cell cycle progression were significantly enriched in glioma cells with high SOX9 expression. SOX9 downregulation decreased cyclin D1, CDK4 expression and Rb phosphorylation, which correlated with a reduced population of cells in the S phase and suppressed growth. SOX9, as an oncogene, is highly expressed in gliomas and may be potential indicators of a poor prognosis in glioma patients. SOX9 knockdown may suppress cancer cell growth by inducing cell cycle arrest, which suggests that SOX9 is a potential therapeutic target in glioma.

SUBMITTER: Gao J

PROVIDER: S-EPMC4637535 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Decreased expression of SOX9 indicates a better prognosis and inhibits the growth of glioma cells by inducing cell cycle arrest.

Gao Jing J Zhang Jia-Yi JY Li Yu-Hong YH Ren Fu F

International journal of clinical and experimental pathology 20150901 9

Deregulation of SOX9 expression has been detected in various human cancer tissues; however, the functional role of SOX9 expression has not been fully elucidated in glioma. SOX9 expression in glioma tissues was analyzed using public tumor datasets and quantitative reverse transcription polymerase chain reaction. The association of SOX9 expression with clinical prognosis in glioma patients was analyzed by examining publically available microarray profiling datasets. The functional roles of SOX9 in ...[more]

PMID: 26617720

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Project description:Glioma accounts for the majority of primary malignant brain tumors in adults and is highly aggressive. Although various therapeutic approaches have been applied, outcomes of glioma treatment remain poor. Acquiring a better understanding of the pathogenic mechanisms is essential to the design of effective therapeutic strategies. Previous studies have found that miR-520d-5p was negatively correlated with glioma grade, but its role and mechanism in glioma progression remain largely unknown. In the present study, we reported that miR-520d-5p directly targeted the Pituitary Tumor Transforming Gene 1 (PTTG1) and functioned as a tumor-suppressor in glioma. The expression of miR-520d-5p in glioma cells and specimens were detected by Quantitative reverse transcription-PCR and Fluorescence in situ hybridization (FISH). The effects of miR-520d-5p on glioma progression was examined by cell-counting kit 8, colony formation, 5-ethynyl-2-deoxyuridine (EDU) and flow cytometry assays. Using bioinformatics and luciferase reporter assays, we identified PTTG1 as a novel and direct target of miR-520d-3p. A xenograft model was used to study the effect of miR-520d-5p on tumor growth and angiogenesis. We found that miR-520d-5p expression was significantly decreased in glioma cell lines and tissues. Overexpression of miR-520d-5p showed a significant inhibitory effect on cell proliferation and accompanied cell cycle G0/G1 arrest in U87-MG and LN229 glioma cells. PTTG1 was a novel and direct target of miR-520d-5p, and the protein expression of PTTG1 was markedly reduced after overexpression of miR-520d-5p in U87-MG and LN229 cells. Overexpression of PTTG1 reversed the inhibitory effect of miR-520d-5p on glioma cell proliferation. In vivo studies confirmed that miR-520d-5p overexpression retarded the growth of U87 xenograft tumors, which was accompanied by reduced expression of PTTG1. In conclusion, these results provide compelling evidence that miR-520d-5p functions as an anti-onco-miRNA, which is important in inhibiting cell proliferation in GBM, and its anti-oncogenic effects are mediated chiefly through direct suppression of PTTG1 expression. Therefore, we suggest that miR-520d-5p is a potential candidate for the prevention of glioblastoma.

Dataset Information

Decreased expression of SOX9 indicates a better prognosis and inhibits the growth of glioma cells by inducing cell cycle arrest.

Publications

Decreased expression of SOX9 indicates a better prognosis and inhibits the growth of glioma cells by inducing cell cycle arrest.

Similar Datasets

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