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

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.

• Authors: Satoru Itani, Toshiyuki Kunisada, Yuki Morimoto, Aki Yoshida, Tsuyoshi Sasaki, Sachio Ito, Mamoru Ouchida, Shinsuke Sugihara, Kenji Shimizu, Toshifumi Ozaki
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 138 Issue 9 Pg. 1501-9 (Sep 2012) ISSN: 1432-1335 [Electronic] Germany
• PMID: 22526161 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Regulatory Proteins
• MIRN21 microRNA, human
• MicroRNAs
• PDCD4 protein, human
• RNA-Binding Proteins

Topics

• Apoptosis Regulatory Proteins (genetics, metabolism)
• Blotting, Western
• Cell Line, Tumor
• Cell Transformation, Neoplastic (genetics)
• Cluster Analysis
• Disease Progression
• Gene Expression Profiling
• Gene Knockdown Techniques
• Humans
• MicroRNAs (genetics)
• Nerve Sheath Neoplasms (genetics, metabolism, pathology)
• Neurofibroma (genetics, metabolism)
• Oligonucleotide Array Sequence Analysis
• RNA-Binding Proteins (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction