title: Prognostic impact of microRNA-145 down-regulation in adult T-cell leukemia/lymphoma.
abstract: Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive tumor caused by human T-cell leukemia virus type 1. MicroRNAs (miRNAs) are closely involved in the development and progression of various tumors. Here we investigated the dysregulation of miRNAs in ATL and its clinical significance. Studies using miRNA arrays and subsequent real-time reverse transcription polymerase chain reaction showed that, in the 9 ATL cell lines examined, 1 miRNA was consistently up-regulated, whereas another 3 were consistently down-regulated, compared with normal CD4-positive lymphocytes. Next, we analyzed the prognostic impact of these 4 miRNAs in patients with aggressive-type ATL (n = 40). Of the 4 dysregulated miRNAs selected, 3 (miR-130b higher expression, miR-145 lower expression, and miR-223 lower expression) were significantly associated with a worsened overall patient survival. We found that expressions of these 3 miRNAs were correlated with each other. To clarify which of the 3 had the most significant impact on overall survival, we performed a multivariate prognostic analysis that included these 3 miRNAs, and only miR-145 lower expression was selected as an independent risk factor (P = .0005). When overexpressed in an ATL cell line in vitro, miR-145 specifically inhibited tumor cell growth. In conclusion, our study suggests that miR-145 down-regulation provides a growth advantage in ATL and is highly associated with a worsened prognosis for patients with ALT. Hence, miR-145 may be a useful prognostic marker and a potential therapeutic target for ATL.
authors.affiliation: Department of Anatomic Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
authors.forename: Hongjing
authors.initials: H
authors.lastname: Xia
authors.affiliation: Department of Anatomic Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
authors.forename: Mineyoshi
authors.initials: M
authors.lastname: Aoyama
authors.affiliation: Department of Anatomic Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Sato
authors.affiliation: Department of Anatomic Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Masaki
authors.affiliation: Department of Anatomic Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ge
authors.affiliation: Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ri
authors.affiliation: Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishida
authors.affiliation: Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan; Department of Tumor Immunology, Aichi Medical University School of Medicine, Nagakute 480-1195, Japan.
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Ueda
authors.affiliation: Department of Hematology, Imamura Bun-in Hospital, Kagoshima 890-0064, Japan.
authors.forename: Atae
authors.initials: A
authors.lastname: Utsunomiya
authors.affiliation: Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Asai
authors.affiliation: Department of Anatomic Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan. Electronic address: hinagaki@med.nagoya-cu.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inagaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000401:mortality; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; C541010:MIRN145 microRNA, human; D035683:MicroRNAs
keywords: Adult T-cell leukemia/lymphoma; Array analysis; MicroRNAs; Prognosis; miR-145