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AMCoR:Asahikawa Medical University Collection and Research (旭川医科大学学術成果リポジトリ)は、本学で生産された電子的な知的生産物(学術雑誌論文の原稿・教材・学術資料など)を保存し、原則的に無償で発信するためのインターネット上の保管庫です。

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閲覧数:911
ID 23963825
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タイトル Downregulation of miR-15a due to LMP1 promotes cell proliferation and predicts poor prognosis in nasal NK/T-cell lymphoma.
著者
駒林, 優樹 (Komabayashi, Yuki)
岸部, 幹 (Kishibe, Kan)
長門, 利純 (Nagato, Toshihiro)
上田, 征吾 (Ueda, Seigo)
高原, 幹 (Takahara, Miki)
原渕, 保明 (Harabuchi, Yasuaki)
上位タイトル
American journal of hematology Vol.89, No.1  (2014. 1) ,p.25- 33
識別番号
ISSN
0361-8609
DOI 10.1002/ajh.23570.
URI http://onlinelibrary.wiley.com/doi/10.1002/ajh.23570/full
その他
PMID:23963825
抄録 Nasal NK/T-cell lymphoma (NNKTL) is an Epstein-Barr virus (EBV)-associated malignancy and has distinct clinical and histological features. However, its genetic features are hitherto unclear. MicroRNAs (miRNAs) play a crucial role in the pathogenesis of several malignancies via regulating gene expression. In this study, we investigated whether the specific microRNAs were related to the tumor behaviors in NNKTL. MiRNA array and Quantitative RT-PCR analyses revealed that miR-15a was expressed at a much lower level in NNKTL cells (SNK-1, SNK-6, and SNT-8) than in normal peripheral NK cells and EBV-negative NK cell line KHYG-1. Quantitative PCR and western blot analyses showed that the expression of MYB and cyclin D1, which are validated targets of miR-15a, was higher in NNKTL cells. Transfection of NNKTL cells (SNK-6 and SNT-8) with a miR-15a precursor decreased MYB and cyclin D1 levels, thereby blocking G1/S transition and cell proliferation. Knockdown of EBV-encoded latent membrane protein 1 (LMP1) significantly increased miR-15a expression in SNK-6 cells. In NNKTL tissues, we found that reduced miR-15a expression, which correlated with MYB and cyclin D1 expression, was associated with poor prognosis of NNKTL patients. These data suggest that downregulation of miR-15a, possibly due to LMP1, implicates in the pathogenesis of NNKTL by inducing cell proliferation via MYB and cyclin D1. Thus, miR-15a could be a potential target for antitumor therapy and a prognostic predictor for NNKTL.
キーワード
Nasal natural killer/T cell lymphoma
microRNA-15a
Epstein-Barr virus
v-myb myeloblastosis viral oncogene homolog
cyclin D1
Epstein-Barr virus latent membrane protein 1
言語
eng
資源タイプ text
ジャンル Journal Article
著者版フラグ author
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/ Public / 国外雑誌論文
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