Long Non-Coding Rna Part1 Exerts Tumor Suppressive Functions In Glioma Via Sponging Mir-190a-3p And Inactivation Of Pten/Akt Pathway

ONCOTARGETS AND THERAPY(2020)

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摘要
Background: Glioma is the most commonly diagnosed primary brain tumor. Dysregulation of long non-coding RNA (lncRNA) is associated with initiation and development of various cancer types including glioma.Methods: The relative expression of lncRNA was analyzed by real time-quantitative polymerase chain reaction (RT-qPCR). Cell counting kit (CCK-8) and flow cytometry analysis were applied to explore the role of prostate androgen-regulated transcript 1 (PART1) in glioma cell lines. Luciferase reporter assay, Western blotting and RT-qPCR were used to investigate the association between PART1, miR-190a-3p and phosphatase and tensin homolog deleted on chromosome ten (PTEN) in glioma cell lines.Results: In the present study, we elucidated a pivotal role and molecular mechanism of lncRNA PART1 in glioma cell lines. It was found that PART1 was significantly down-regulated in glioma tissues compared to normal tissues according to TCGA data and our RT-qPCR results. The cell-based assays showed that PART1 suppressed cell proliferation and triggered cell apoptosis in glioma cell lines. PART1 inactivated PI3K/AKT cascade in glioma cell lines. Transfection of constitutively activated AKT (Myr-AKT) reversed PART1 induced cell apoptosis and cell growth arrest. The bioinformatic analysis suggested that miR-190a-3p might bind to PART1. In the dual luciferase reporter assay, we validated that PART1 directly bound to miR-190a-3p in glioma cell lines. Furthermore, there was a reciprocal repression between PART1 and miR-190-3p. In addition, PART1 upregulated PTEN and inactivated PI3K/AKT pathway in glioma cell lines. Moreover, silencing of PTEN reversed PART1 overexpression induced cell growth arrest and apoptosis. In glioma tissues, the Pearson Correlation analysis showed that there was a strong-positive correlation between PART1 level and PTEN mRNA level.Conclusion: Taken together, the current study revealed a PART1/miR-190a-3p/PTEN/PI3K/AKT axis in glioma and provided novel insights for understanding the complex lncRNA-miRNA network in glioma.
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关键词
prostate androgen-regulated transcript 1, microRNA-190a-3p, PI3K/AKT signaling, glioma
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