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Journal of Neuro-Oncology

, Volume 112, Issue 1, pp 27–37 | Cite as

miRNA-mediated tumor specific delivery of TRAIL reduced glioma growth

  • Yongli BoEmail author
  • Guocai Guo
  • Weicheng Yao
Laboratory Investigation

Abstract

As an aggressive cancer with high morbidity, malignant glioma always has a poor prognosis even after surgery, chemotherapy and radiotherapy. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) shows a strong apoptosis-inducing effect on a variety of cancer cells including glioma. However so far, TRAIL delivery mediated by adenoviral vectors lacks tumor specificity and thus has cytotoxicity to normal cells. To improve the tumor-specificity of adenovirus-mediated TRAIL delivery, we utilized miR-124, miR-128, miR-146b and miR-218 to restrict its expression to within glioma cells. qPCR assay showed that expression of these four miRNAs was greatly downregulated in glioma in comparison with normal brain tissue. Luciferase reporter assay confirmed that miR-124, miR-128, miR-146b and miR-218 conferred exogenous gene expression with glioma-specificity. By inserting miRNA response elements (MREs) of these miRNAs into the downstream of TRAIL on adenoviral vectors, TRAIL was highly expressed in glioma cells, but not in normal brain cells. Cell viability and immunoblotting assays and FACS analysis showed that cytotoxicity and apoptosis elicited by TRAIL was only observed in glioma cells, rather than normal brain cells. Animal experiments also showed that MREs-regulated TRAIL delivery reduced the growth of glioma xenograft. In this study, we proved that miRNA-mediated tumor specific delivery of TRAIL was able to inhibit the survival of glioma cells and reduce the growth of glioma in vivo.

Keywords

Glioma Adenovirus miRNA Specificity TRAIL 

Notes

Acknowledgments

We appreciated generous providing of adenoviruses by Dr. Zhao in General Hospital of Chengdu Military Area Command of Chinese PLA, Chengdu, China and plasmids by Dr. Ma, Ocean University of China, Qingdao, China.

Conflict of interest

None.

Supplementary material

11060_2012_1033_MOESM1_ESM.ppt (626 kb)
Supplementary material 1 (PPT 626 kb)
11060_2012_1033_MOESM2_ESM.docx (11 kb)
Supplementary material 2 (DOCX 11 kb)

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of NeurosurgeryThe Affiliated Hospital of Medical College, Qingdao UniversityQingdaoChina

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