title: miR-133 regulates Evi1 expression in AML cells as a potential therapeutic target.
abstract: The Ecotropic viral integration site 1 (Evi1) is a zinc finger transcription factor, which is located on chromosome 3q26, over-expression in some acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Elevated Evi1 expression in AML is associated with unfavorable prognosis. Therefore, Evi1 is one of the strong candidate in molecular target therapy for the leukemia. MicroRNAs (miRNAs) are small non-coding RNAs, vital to many cell functions that negatively regulate gene expression by translation or inducing sequence-specific degradation of target mRNAs. As a novel biologics, miRNAs is a promising therapeutic target due to its low toxicity and low cost. We screened miRNAs which down-regulate Evi1. miR-133 was identified to directly bind to Evi1 to regulate it. miR-133 increases drug sensitivity specifically in Evi1 expressing leukemic cells, but not in Evi1-non-expressing cells The results suggest that miR-133 can be promising therapeutic target for the Evi1 dysregulated poor prognostic leukemia.
authors.affiliation: Department of Hematological Malignancy, Institute of Medical Science, Tokai University, 143 Shimokasuya, Isehara, Kanagawa 259-1193 Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Intractable Diseases, Institute of National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655 Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Nephrology and Endocrinology, the University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 Japan.
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Oba
authors.affiliation: Department of Hematology/ Oncology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 Japan.
authors.forename: Toyotaka
authors.initials: T
authors.lastname: Kawamata
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, the University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 Japan.
authors.forename: Akihide
authors.initials: A
authors.lastname: Yoshimi
authors.affiliation: Department of Hematological Malignancy, Institute of Medical Science, Tokai University, 143 Shimokasuya, Isehara, Kanagawa 259-1193 Japan.
authors.forename: Natsumi
authors.initials: N
authors.lastname: Kurosaki
authors.affiliation: Department of Hematology/ Oncology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Yokoyama
authors.affiliation: Department of Hematology / Oncology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara, Kanagawa 259-1193 Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Matsushita
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, the University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 Japan.
authors.forename: Mineo
authors.initials: M
authors.lastname: Kurokawa
authors.affiliation: Department of Hematology/ Oncology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 Japan.
authors.forename: Arinobu
authors.initials: A
authors.lastname: Tojo
authors.affiliation: Department of Hematology / Oncology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara, Kanagawa 259-1193 Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ando
authors.affiliation: Department of Medical Science, Faculty of Medicine, University of Miyazaki, 5200 Kiyotakecho Kihara, Miyazaki-city, Miyazaki 889-1692 Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Morishita
authors.affiliation: Department of Biosciences, School of Science, Kitasato University 1-15-1, Kitasato, Minami-ku, Sagamihara, Knagawa 252-0373 Japan.
authors.forename: Koko
authors.initials: K
authors.lastname: Katagiri
authors.affiliation: Department of Hematological Malignancy, Institute of Medical Science, Tokai University, 143 Shimokasuya, Isehara, Kanagawa 259-1193 Japan.|Department of Hematology / Oncology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara, Kanagawa 259-1193 Japan.|Japan Science and Technology Agency (JST) Science Plaza 5-3, Yonbancho, Chiyoda-ku, Tokyo 102-8666 Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Kotani
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics*; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D000074008:MDS1 and EVI1 Complex Locus Protein; D051379:Mice; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D008954:Models, Biological; D011519:Proto-Oncogenes / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000737:chemistry; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D014157:Transcription Factors