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MicroRNA-21 correlates with tumorigenesis in malignant peripheral nerve sheath tumor (MPNST) via programmed cell death protein 4 (PDCD4)

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Abstract

Purpose

We investigated the miRNA profile in peripheral nerve tumors and clarified the involvement of miRNA in the development and progression of MPNST in comparison with neurofibroma (NF). In addition, we attempted to seek associations between the miRNA and their potential targets in MPNST.

Methods

Global miRNA expression profiling was investigated for clinical samples of 6 MPNSTs and 6 NFs. As detected by profiling analysis, the expressions of miR-21 in clinical samples of 12 MPNSTs, 11 NFs, and 5 normal nerves, and 3 MPNST cell lines were compared using quantitative real-time reverse transcription PCR. MPNST cell line (YST-1) was transfected with miR-21 inhibitor to study its effects on cell proliferation, caspase activity, and the expression of miR-21 targets.

Results

Analysis of miRNA expression profiles in MPNST and NF revealed significantly altered expression levels of nine miRNAs, one of those, miR-21, and its putative target, programmed cell death protein 4 (PDCD4), were selected for further studies. miR-21 expression level in MPNST was significantly higher than that in NF (P < 0.05). In MPNST cells, transfection of miR-21 inhibitor significantly increased caspase activity (P < 0.01), significantly suppressed cell growth (P < 0.05), and upregulated protein level of PDCD4, indicating that miR-21 inhibitor could induce cell apoptosis of MPNST cells.

Conclusions

These results suggest that miR-21 plays an important role in MPNST tumorigenesis and progression through its target, PDCD4. MiR-21 and PDCD4 may be candidate novel therapeutic targets against the development or progression of MPNSTs.

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Acknowledgments

This work was supported in part by Grants-in-Aid for Clinical Cancer Research and Grants-in-Aid for Cancer Research (14S-4 and -5) from the Ministry of Health, Labor and Welfare.

Conflict of interest

None declared.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Satoru Itani, Yuki Morimoto, Aki Yoshida, Tsuyoshi Sasaki & Toshifumi Ozaki

  2. Department of Medical Materials for Musculoskeletal Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Toshiyuki Kunisada

  3. Department of Molecular Genetics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Sachio Ito, Mamoru Ouchida & Kenji Shimizu

  4. Department of Orthopaedic Surgery, Shikoku Cancer Center, Matsuyama, Japan

    Shinsuke Sugihara

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  1. Satoru Itani
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  2. Toshiyuki Kunisada
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  3. Yuki Morimoto
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Correspondence to Toshiyuki Kunisada.

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Itani, S., Kunisada, T., Morimoto, Y. et al. MicroRNA-21 correlates with tumorigenesis in malignant peripheral nerve sheath tumor (MPNST) via programmed cell death protein 4 (PDCD4). J Cancer Res Clin Oncol 138, 1501–1509 (2012). https://doi.org/10.1007/s00432-012-1223-1

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  • DOI: https://doi.org/10.1007/s00432-012-1223-1

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