Tumor necrosis factor‑related apoptosis‑inducing ligand induces cytotoxicity specific to osteosarcoma by microRNA 
response elements

Xiao,Fei; Chen,Juwu; Lian,Chuanju; Han,Pengchao; Zhang,Chaoyang

doi:10.3892/mmr.2014.2710

January-2015 Volume 11 Issue 1

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January-2015 Volume 11 Issue 1

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Article

Tumor necrosis factor‑related apoptosis‑inducing ligand induces cytotoxicity specific to osteosarcoma by microRNA response elements

Authors:
- Fei Xiao
- Juwu Chen
- Chuanju Lian
- Pengchao Han
- Chaoyang Zhang
View Affiliations / Copyright

Affiliations: Department of Emergency Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Pages: 739-745
|
Published online on: October 20, 2014

https://doi.org/10.3892/mmr.2014.2710
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Abstract

As the most common primary bone neoplasm, osteosarcoma is highly aggressive and represents a high risk to human health. Biological agents, including tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL), are considered promising therapeutic strategies for osteosarcoma. The current issue limiting the application of TRAIL gene therapy is that normal cells are also affected due to the lack of tumor selectivity. The present study aimed to employ the miRNA response elements (MREs) of microRNA (miR)‑34 and miR‑122, which are tumor suppressors, to enable the selective expression of TRAIL by adenoviral vectors in osteosarcoma cells. The results revealed that miR‑34 and miR‑122 were underexpressed in osteosarcoma tissues, compared with normal tissues. The MREs of miR‑34 and miR‑122 ensured that the luciferase gene was expressed selectively in osteosarcoma cells. Adenovirus (Ad)‑TRAIL‑34‑122, which expressed TRAIL in an miR‑34 and miR‑122‑regulated manner, selectively expressed TRAIL in the osteosarcoma cells assessed, which was detected using reverse transcription quantitative polymerase chain reaction, immunoblotting and ELISA. Apoptosis and cytotoxicity were also detected in the osteosarcoma cells, compared with the normal cells. Animal experiments further indicated that Ad‑TRAIL‑34‑122 was able to reduce the growth of osteosarcoma xenografts without toxicity to the liver. In conclusion, the present study identified a novel miRNA‑regulated biological cancer therapy against osteosarcoma, which is tumor selective and may be promising for future clinical treatment.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Tumor necrosis factor‑related apoptosis‑inducing ligand induces cytotoxicity specific to osteosarcoma by microRNA response elements

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