Glioblastoma multiforme (GBM) is the most aggressive and prevalent brain tumor in adults. The circRNAderived from CLSPN (hsa_circ_0011591, circCLSPN) is remarkably upregulated in GBM; however itsfunctional role was uncovered yet. First, we examined expression of circCLSPN using GSE109569 databaseand RT-qPCR, and circCLSPN level was upregulated in human GBM tumor tissues and cells (A172 andLN18); moreover, circCLSPN showed a stable structure stability. Then, a series of loss-of-functional experimentswere performed using CCK-8 assay, colony formation assay, flow cytometry, scratch wound assay, andtranswell assay. Consequently, circCLSPN silencing suppressed cell viability, colony formation ability, cellcycle progression, migration, and invasion of A172 and LN18 cells in vitro, and promoted apoptosis rate.Allied with those were decreased B cell lymphoma-2 (Bcl-2), matrix metalloproteinase-2 (MMP2) and MMP9expression, and elevated Bcl-2-associated X protein (Bax) level. According to dual-luciferase reporter assayand RNA pull-down assay, miR-370-3p was identified to be targeted and sponged by circCLSPN, and furthertargeted and negatively regulated USP39. Functionally, overexpressing miR-370-3p could mimic in vitroeffects of circCLSPN interference. Rescue experiments revealed that blocking miR-370-3p could partiallyreverse the suppression of circCLSPN knockdown on cell growth, migration and invasion, and role of miR-370-3p overexpression was abrogated by restoring USP39. In vivo, circCLSPN knockdown hindered tumorgrowth of LN18 cells by affecting miR-370-3p, USP39, MMP2 and MMP9 expression. In conclusion,circCLSPN elicited an oncogenic role in tumorigenesis and malignant progression of human GBM cellsthrough circCLSPN-miR-370-3p-USP39 pathway.
Volume 46, 2020
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