title: Downregulation of miR-15a due to LMP1 promotes cell proliferation and predicts poor prognosis in nasal NK/T-cell lymphoma.
abstract: 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.
authors: Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Asahikawa, Midorigaoka-higashi 2-1-1-1, Asahikawa, Japan.
authors: Yuki
authors: Y
authors: Komabayashi
authors: Kan
authors: K
authors: Kishibe
authors: Toshihiro
authors: T
authors: Nagato
authors: Seigo
authors: S
authors: Ueda
authors: Miki
authors: M
authors: Takahara
authors: Yasuaki
authors: Y
authors: Harabuchi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D054391:Lymphoma, Extranodal NK-T-Cell / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D020626:Oncogene Proteins v-myb / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; C505361:MIRN15 microRNA, human; D035683:MicroRNAs; D020626:Oncogene Proteins v-myb; D014763:Viral Matrix Proteins; D019938:Cyclin D1