Exosomal miR-221 targets DNM3 to induce tumor progression and temozolomide resistance in glioma

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• 作者：Jian-Kai Yang ; Ji-Peng Yang ; Jing Tong ; Shi-Yuan Jing ; Bo Fan…
• 关键词：Exosome ; Glioma ; MiR ; 221 ; DNM3 ; RELA ; Drug resistance
• 刊名：Journal of Neuro-Oncology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：131
• 期：2
• 页码：255-265
• 全文大小：
• 刊物类别：Medicine
• 刊物主题：Oncology; Neurology;
• 出版者：Springer US
• ISSN：1573-7373
• 卷排序：131

文摘

MicroRNA is an important regulator of glioblastoma. This study aims at validating microRNA-221 (miR-221) as a biomarker for glioblastoma, and understanding how miR-221 regulates glioblastoma progression. Using clinical samples, miR-221 expression was analyzed by quantitative reverse-transcriptase PCR (qPCR). SHG-44 cells were treated with anti-miR-221 or U87MG-derived exosomes followed by monitoring changes in cell viability, migration and temozolomide (TMZ) resistance. Bioinformatics approach was used to identify targets of miR-221. The interaction between miR-221 and its target, DNM3 gene, was studied with dual-luciferase reporter assay, Spearman’s correlation analysis, and western blotting. To verify that RELA regulates miR-221 expression, RELA-expressing vector or shRNA was introduced into SHG-44 cells and its effect on miR-221 expression was monitored. Both tissue-level and exosomal miR-221 expression increased with glioma grades. In SHG-44 cells, downregulating miR-221 expression inhibited cell proliferation, migration, and TMZ resistance, whereas incubation with U87MG-derived exosomes exerted tumor-promoting effects. DNM3 gene is a target of miR-221. RELA induced miR-221 expression. In glioma, elevated miR-221 expression is a biomarker for glioma. DNM3 is a target of miR-221 and RELA regulates miR-221 expression. The RELA/miR-221 axis is a target for glioma diagnosis and therapy.