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

Satoru Itani, Toshiyuki Kunisada, Yuki Morimoto, Aki Yoshida, Tsuyoshi Sasaki, Sachio Itou, Mamoru Oouchida, Shinsuke Sugihara, Kenji Shimizu, Toshihumi Ozaki

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1501-1509
Number of pages9
JournalJournal of Cancer Research and Clinical Oncology
Volume138
Issue number9
DOIs
Publication statusPublished - Sep 2012

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Apoptosis Regulatory Proteins
Neurilemmoma
MicroRNAs
Carcinogenesis
Neurofibroma
Tumor Cell Line
Peripheral Nervous System Neoplasms
Caspases
Reverse Transcription
Cell Proliferation
Apoptosis

Keywords

  • Malignant peripheral nerve sheath tumor
  • MicroRNA
  • MiR-21
  • PDCD4

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

MicroRNA-21 correlates with tumorigenesis in malignant peripheral nerve sheath tumor (MPNST) via programmed cell death protein 4 (PDCD4). / Itani, Satoru; Kunisada, Toshiyuki; Morimoto, Yuki; Yoshida, Aki; Sasaki, Tsuyoshi; Itou, Sachio; Oouchida, Mamoru; Sugihara, Shinsuke; Shimizu, Kenji; Ozaki, Toshihumi.

In: Journal of Cancer Research and Clinical Oncology, Vol. 138, No. 9, 09.2012, p. 1501-1509.

Research output: Contribution to journalArticle

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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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AU - Itani, Satoru

AU - Kunisada, Toshiyuki

AU - Morimoto, Yuki

AU - Yoshida, Aki

AU - Sasaki, Tsuyoshi

AU - Itou, Sachio

AU - Oouchida, Mamoru

AU - Sugihara, Shinsuke

AU - Shimizu, Kenji

AU - Ozaki, Toshihumi

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N2 - 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.

AB - 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.

KW - Malignant peripheral nerve sheath tumor

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KW - PDCD4

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