title: miR-155, a Modulator of FOXO3a Protein Expression, Is Underexpressed and Cannot Be Upregulated by Stimulation of HOZOT, a Line of Multifunctional Treg.
abstract: MicroRNAs (miRNAs) play important roles in regulating post-transcriptional gene repression in a variety of immunological processes. In particular, much attention has been focused on their roles in regulatory T (Treg) cells which are crucial for maintaining peripheral tolerance and controlling T cell responses. Recently, we established a novel type of human Treg cell line, termed HOZOT, multifunctional cells exhibiting a CD4(+)CD8(+) phenotype. In this study, we performed miRNA profiling to identify signature miRNAs of HOZOT, and therein identified miR-155. Although miR-155 has also been characterized as a signature miRNA for FOXP3(+) natural Treg (nTreg) cells, it was expressed quite differently in HOZOT cells. Under both stimulatory and non-stimulatory conditions, miR-155 expression remained at low levels in HOZOT, while its expression in nTreg and conventional T cells remarkably increased after stimulation. We next searched candidate target genes of miR-155 through bioinformatics, and identified FOXO3a, a negative regulator of Akt signaling, as a miR-155 target gene. Further studies by gain- and loss-of-function experiments supported a role for miR-155 in the regulation of FOXO3a protein expression in conventional T and HOZOT cells.
authors.affiliation: Cell Biology Institute, Research Center, Hayashibara Biochemical Laboratories Inc., Okayama, Japan. m_yamamoto@hayashibara.co.jp
authors.forename: Mayuko
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Eisaku
authors.initials: E
authors.lastname: Kondo
authors.forename: Makoto
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Akira
authors.initials: A
authors.lastname: Harashima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Otani
authors.forename: Kazue
authors.initials: K
authors.lastname: Tsuji-Takayama
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Yamasaki
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kumon
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kibata
authors.forename: Shuji
authors.initials: S
authors.lastname: Nakamura
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D015536:Down-Regulation; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000235:genetics* / Q000502:physiology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D046228:Microarray Analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000502:physiology*; D054928:Validation Studies as Topic
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C524942:MIRN155 microRNA, human; D035683:MicroRNAs