2023/10/21 更新

写真a

ヨシノ セイコ
芳野 聖子
YOSHINO Seiko
所属
大学院医学系研究科 附属医学教育研究支援センター 先端領域支援部門 助教
職名
助教

学位 1

  1. 博士(生命科学) ( 2013年3月   東京大学 ) 

 

論文 11

  1. Distinct microRNA signature and suppression of ZFP36L1 define ASCL1-positive lung adenocarcinoma. 査読有り

    Enokido T, Horie M, Yoshino S, Suzuki HI, Matsuki R, Brunnström H, Micke P, Nagase T, Saito A, Miyashita N

    Molecular cancer research : MCR     2023年10月

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    記述言語:英語  

    DOI: 10.1158/1541-7786.MCR-23-0229

    PubMed

  2. Systematic characterization of seed overlap microRNA cotargeting associated with lupus pathogenesis 査読有り

    Kitai Hiroki, Kato Noritoshi, Ogami Koichi, Komatsu Shintaro, Watanabe Yu, Yoshino Seiko, Koshi Eri, Tsubota Shoma, Funahashi Yoshio, Maeda Takahiro, Furuhashi Kazuhiro, Ishimoto Takuji, Kosugi Tomoki, Maruyama Shoichi, Kadomatsu Kenji, Suzuki Hiroshi I

    BMC BIOLOGY   20 巻 ( 1 ) 頁: 248   2022年11月

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    記述言語:英語   出版者・発行元:BMC Biology  

    Background: Combinatorial gene regulation by multiple microRNAs (miRNAs) is widespread and closely spaced target sites often act cooperatively to achieve stronger repression (“neighborhood” miRNA cotargeting). While miRNA cotarget sites are suggested to be more conserved and implicated in developmental control, the pathological significance of miRNA cotargeting remains elusive. Results: Here, we report the pathogenic impacts of combinatorial miRNA regulation on inflammation in systemic lupus erythematosus (SLE). In the SLE mouse model, we identified the downregulation of two miRNAs, miR-128 and miR-148a, by TLR7 stimulation in plasmacytoid dendritic cells. Functional analyses using human cell lines demonstrated that miR-128 and miR-148a additively target KLF4 via extensively overlapping target sites (“seed overlap” miRNA cotargeting) and suppress the inflammatory responses. At the transcriptome level, “seed overlap” miRNA cotargeting increases susceptibility to downregulation by two miRNAs, consistent with additive but not cooperative recruitment of two miRNAs. Systematic characterization further revealed that extensive “seed overlap” is a prevalent feature among broadly conserved miRNAs. Highly conserved target sites of broadly conserved miRNAs are largely divided into two classes—those conserved among eutherian mammals and from human to Coelacanth, and the latter, including KLF4-cotargeting sites, has a stronger association with both “seed overlap” and “neighborhood” miRNA cotargeting. Furthermore, a deeply conserved miRNA target class has a higher probability of haplo-insufficient genes. Conclusions: Our study collectively suggests the complexity of distinct modes of miRNA cotargeting and the importance of their perturbations in human diseases.

    DOI: 10.1186/s12915-022-01447-4

    Web of Science

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    PubMed

  3. The molecular understanding of super-enhancer dysregulation in cancer 査読有り

    Yoshino Seiko, Suzuki Hiroshi I.

    NAGOYA JOURNAL OF MEDICAL SCIENCE   84 巻 ( 2 ) 頁: 216 - 229   2022年5月

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    担当区分:筆頭著者   記述言語:英語   出版者・発行元:Nagoya Journal of Medical Science  

    Abnormalities in the regulation of gene expression are associated with various pathological conditions. Among the distal regulatory elements in the genome, the activation of target genes by enhancers plays a central role in the formation of cell type–specific gene expression patterns. Super-enhancers are a subclass of enhancers that frequently contain multiple enhancer-like elements and are characterized by dense binding of master transcription factors and Mediator complexes and high signals of active histone marks. Superenhancers have been studied in detail as important regulatory regions that control cell identity and contribute to the pathogenesis of diverse diseases. In cancer, super-enhancers have multifaceted roles by activating various oncogenes and other cancer-related genes and shaping characteristic gene expression patterns in cancer cells. Alterations in super-enhancer activities in cancer involve multiple mechanisms, including the dysregulation of transcription factors and the super-enhancer–associated genomic abnormalities. The study of super-enhancers could contribute to the identification of effective biomarkers and the development of cancer therapeutics targeting transcriptional addiction. In this review, we summarize the roles of super-enhancers in cancer biology, with a particular focus on hematopoietic malignancies, in which multiple super-enhancer alteration mechanisms have been reported.

    DOI: 10.18999/nagjms.84.2.216

    Web of Science

    Scopus

    PubMed

  4. BCL11A promotes myeloid leukemogenesis by repressing PU.1 target genes. 査読有り

    Sunami Y, Yokoyama T, Yoshino S, Takahara T, Yamazaki Y, Harada H, Nakamura T

    Blood advances   6 巻 ( 6 ) 頁: 1827 - 1843   2022年3月

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    記述言語:英語  

    DOI: 10.1182/bloodadvances.2021004558

    PubMed

  5. Trib1 promotes the development of acute myeloid leukemia in a Ts1Cje mouse model of Down syndrome. 査読有り

    Yoshino S, Tanaka M, Sunami Y, Takahara T, Yamazaki Y, Homme M, Niibori-Nambu A, Osato M, Minami T, Ishihara K, Nakamura T

    Leukemia   36 巻 ( 2 ) 頁: 558 - 561   2022年2月

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    担当区分:筆頭著者   記述言語:英語  

    DOI: 10.1038/s41375-021-01384-1

    PubMed

  6. Trib1 promotes acute myeloid leukemia progression by modulating the transcriptional programs of Hoxa9. 査読有り

    Yoshino S, Yokoyama T, Sunami Y, Takahara T, Nakamura A, Yamazaki Y, Tsutsumi S, Aburatani H, Nakamura T

    Blood   137 巻 ( 1 ) 頁: 75 - 88   2021年1月

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    担当区分:筆頭著者   記述言語:英語  

    DOI: 10.1182/blood.2019004586

    PubMed

  7. EXOSC9 depletion attenuates P-body formation, stress resistance, and tumorigenicity of cancer cells 査読有り 国際誌

    Yoshino Seiko, Matsui Yusuke, Fukui Yuya, Seki Masahide, Yamaguchi Kiyoshi, Kanamori Akane, Saitoh Yurika, Shimamura Teppei, Suzuki Yutaka, Furukawa Yoichi, Kaneko Shuichi, Seiki Motoharu, Murakami Yoshinori, Inoue Jun-ichiro, Sakamoto Takeharu

    SCIENTIFIC REPORTS   10 巻 ( 1 ) 頁: 9275 - 9275   2020年6月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Scientific Reports  

    Cancer cells adapt to various stress conditions by optimizing gene expression profiles via transcriptional and translational regulation. However, whether and how EXOSC9, a component of the RNA exosome complex, regulates adaptation to stress conditions and tumorigenicity in cancer cells remain unclear. Here, we examined the effects of EXOSC9 depletion on cancer cell growth under various stress conditions. EXOSC9 depletion attenuated growth and survival under various stress conditions in cancer cells. Interestingly, this also decreased the number of P-bodies, which are messenger ribonucleoprotein particles (mRNPs) required for stress adaptation. Meanwhile, EXOSC2/EXOSC4 depletion also attenuated P-body formation and stress resistance with decreased EXOSC9 protein. EXOSC9-mediated stress resistance and P-body formation were found to depend on the intact RNA-binding motif of this protein. Further, RNA-seq analyses identified 343 EXOSC9-target genes, among which, APOBEC3G contributed to defects in stress resistance and P-body formation in MDA-MB-231 cells. Finally, EXOSC9 also promoted xenografted tumor growth of MDA-MB-231 cells in an intact RNA-binding motif-dependent manner. Database analyses further showed that higher EXOSC9 activity, estimated based on the expression of 343 target genes, was correlated with poorer prognosis in some cancer patients. Thus, drugs targeting activity of the RNA exosome complex or EXOSC9 might be useful for cancer treatment.

    DOI: 10.1038/s41598-020-66455-2

    Web of Science

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  8. NECAB3 Promotes Activation of Hypoxia-inducible factor-1 during Normoxia and Enhances Tumourigenicity of Cancer Cells 査読有り 国際誌

    Nakaoka Hiroki J., Hara Toshiro, Yoshino Seiko, Kanamori Akane, Matsui Yusuke, Shimamura Teppei, Sato Hiroshi, Murakami Yoshinori, Seiki Motoharu, Sakamoto Takeharu

    SCIENTIFIC REPORTS   6 巻   頁: 22784 - 22784   2016年3月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Scientific Reports  

    Unlike most cells, cancer cells activate hypoxia inducible factor-1 (HIF-1) to use glycolysis even at normal oxygen levels, or normoxia. Therefore, HIF-1 is an attractive target in cancer therapy. However, the regulation of HIF-1 during normoxia is not well characterised, although Mint3 was recently found to activate HIF-1 in cancer cells and macrophages by suppressing the HIF-1 inhibitor, factor inhibiting HIF-1 (FIH-1). In this study, we analysed Mint3-binding proteins to investigate the mechanism by which Mint3 regulates HIF-1. Yeast two-hybrid screening using Mint3 as bait identified N-terminal EF-hand calcium binding protein 3 (NECAB3) as a novel factor regulating HIF-1 activity via Mint3. NECAB3 bound to the phosphotyrosine-binding domain of Mint3, formed a ternary complex with Mint3 and FIH-1, and co-localised with Mint3 at the Golgi apparatus. Depletion of NECAB3 decreased the expression of HIF-1 target genes and reduced glycolysis in normoxic cancer cells. NECAB3 mutants that binds Mint3 but lacks an intact monooxygenase domain also inhibited HIF-1 activation. Inhibition of NECAB3 in cancer cells by either expressing shRNAs or generating a dominant negative mutant reduced tumourigenicity. Taken together, the data indicate that NECAB3 is a promising new target for cancer therapy.

    DOI: 10.1038/srep22784

    Web of Science

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  9. The ERK signaling target RNF126 regulates anoikis resistance in cancer cells by changing the mitochondrial metabolic flux. 査読有り 国際誌

    Yoshino S, Hara T, Nakaoka HJ, Kanamori A, Murakami Y, Seiki M, Sakamoto T

    Cell discovery   2 巻   頁: 16019 - 16019   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/celldisc.2016.19

    PubMed

  10. Hypoxia-inducible factor 1 regulation through cross talk between mTOR and MT1-MMP. 査読有り 国際誌

    Sakamoto T, Weng JS, Hara T, Yoshino S, Kozuka-Hata H, Oyama M, Seiki M

    Molecular and cellular biology   34 巻 ( 1 ) 頁: 30 - 42   2014年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1128/MCB.01169-13

    PubMed

  11. Genetic screening of new genes responsible for cellular adaptation to hypoxia using a genome-wide shRNA library. 査読有り 国際誌

    Yoshino S, Hara T, Weng JS, Takahashi Y, Seiki M, Sakamoto T

    PloS one   7 巻 ( 4 ) 頁: e35590   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1371/journal.pone.0035590

    PubMed

▼全件表示

MISC 5

  1. 生体分子凝集体と染色体外環状DNA

    芳野 聖子、鈴木 洋  

    Bio Clinica38 巻 ( 7 ) 頁: 66 - 71   2023年7月

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    担当区分:筆頭著者  

  2. 第2部5章 デジタルPCRによるmiRNAの測定

    芳野 聖子, 小松 真太郎, 鈴木 洋  

    実験医学部冊「リアルタイム・デジタルPCR実験スタンダード」   頁: 258 - 264   2022年2月

  3. Trib1によるHoxa9転写制御の修飾とAML発症

    中村 卓郎, 芳野 聖子  

    血液内科83 巻 ( 1 ) 頁: 115 - 120   2021年7月

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    記述言語:日本語   出版者・発行元:(有)科学評論社  

  4. Pseudokinase TRIB1による骨髄系腫瘍の発症と進展機構

    芳野 聖子, 中村 卓郎  

    血液内科82 巻 ( 4 ) 頁: 573 - 579   2021年4月

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    記述言語:日本語   出版者・発行元:(有)科学評論社  

  5. Introduce My Article

    芳野 聖子, 中村 卓郎  

    臨床血液61 巻 ( 11 ) 頁: 1634   2020年11月

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    記述言語:日本語  

科研費 4

  1. 染色体外環状DNAによるがん悪性化進展機構の解明と治療標的としての可能性

    研究課題/研究課題番号:22K07210  2022年4月 - 2025年3月

    科学研究費助成事業  基盤研究(C)

    芳野 聖子

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    担当区分:研究代表者 

    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

    近年、がん細胞には染色体外環状DNA(eccDNA)が広範に存在することが報告され、がんの増殖や不均一性との関連が示唆されている。重要なことに、eccDNAを介したがん遺伝子の増幅は、正常組織ではほとんど見られない。一方で、様々ながん種におけるeccDNAの構造の違いやがん細胞の生存・増殖への影響については、依然として不明な点が多く存在する。本研究では、eccDNAを様々ながん種で包括的に解析し、がん細胞における生物学的特性を解明することで、がん治療標的としての可能性を明らかにするとともに、がん特異的な治療薬の同定に繋げることを目的とする。

  2. Trib1のエンハンサーリプログラミングによるAML悪性化機構の解明

    研究課題/研究課題番号:20K16318  2020年4月 - 2022年3月

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    芳野 聖子

  3. 公益財団法人 上原記念生命科学財団 研究奨励金

    2020年 - 2021年

    AMLにおけるTRIB1のスーパーエンハンサー制御

    芳野 聖子

  4. Pseudokinase Trib1によるAMLのエピゲノム修飾

    研究課題/研究課題番号:18K15227  2018年4月 - 2020年3月

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    芳野 聖子

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    急性骨髄性白血病(AML)の発症と進展において、ホメオボックス遺伝子Hoxa9とCCAAT/enhancer-binding protein-α (C/EBPα)は重要な転写因子であるが、Pseudokinase Trib1はその双方の機能を修飾することで更なる悪性化をもたらす。本研究では、Trib1がC/EBPα p42の分解を介して、Hoxa9のDNA結合領域やスーパーエンハンサーを改変することを見出した。また、Trib1/Hoxa9の標的遺伝子としてErgを同定し、BRD4阻害剤JQ1は、in vitro及びin vivoの両方でTrib1/Erg依存的に増殖抑制することを明らかにした。