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

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Abstract

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.

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Acknowledgements

The authors would like to thank Dr. Li-qun Wang, Dr. Zhong-qiang Lv, and Dr. Zong-mao Zhao for their technical advice.

Funding

This study was supported by the Program of Graduate students innovation fund of Hebei Province.

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Authors and Affiliations

  1. Department of Neurosurgery, The Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang, 050000, China

    Jian-Kai Yang, Ji-Peng Yang, Jing Tong, Shi-Yuan Jing, Bo Fan, Feng Wang, Guo-Zhu Sun & Bao-Hua Jiao

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  1. Jian-Kai Yang
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  2. Ji-Peng Yang
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  3. Jing Tong
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  4. Shi-Yuan Jing
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  7. Guo-Zhu Sun
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  8. Bao-Hua Jiao
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Correspondence to Bao-Hua Jiao.

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The protocols approved by the Committee on the Ethics of Animal Experiments of The Second Hospital of Hebei Medical University.

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Yang, JK., Yang, JP., Tong, J. et al. Exosomal miR-221 targets DNM3 to induce tumor progression and temozolomide resistance in glioma. J Neurooncol 131, 255–265 (2017). https://doi.org/10.1007/s11060-016-2308-5

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  • DOI: https://doi.org/10.1007/s11060-016-2308-5

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