RRC ID 75815
Author Itani S, Kunisada T, Morimoto Y, Yoshida A, Sasaki T, Ito S, Ouchida M, Sugihara S, Shimizu K, Ozaki T.
Title MicroRNA-21 correlates with tumorigenesis in malignant peripheral nerve sheath tumor (MPNST) via programmed cell death protein 4 (PDCD4).
Journal J Cancer Res Clin Oncol
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.
Volume 138(9)
Pages 1501-9
Published 2012-9-1
DOI 10.1007/s00432-012-1223-1
PMID 22526161
MeSH Apoptosis Regulatory Proteins / genetics* Apoptosis Regulatory Proteins / 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* Nerve Sheath Neoplasms / metabolism Nerve Sheath Neoplasms / pathology Neurofibroma / genetics Neurofibroma / metabolism Oligonucleotide Array Sequence Analysis RNA-Binding Proteins / genetics* RNA-Binding Proteins / metabolism Reverse Transcriptase Polymerase Chain Reaction
IF 3.656
Human and Animal Cells HS-Sch-2(RCB2230) YST-1(RCB2136) NMS-2(RCB2347)