Updated on 2026/02/10

写真a

 
OKADA Ryu
 
Organization
Graduate School of Medicine Designated Assistant Professor
Title
Designated Assistant Professor

Degree 1

  1. Doctor of Philosophy （ 2024.9   Saitama University ） 

To the head of Degree.▲
 

Papers 7

  1. Synthetic lethality of EZH2 and DNMT Inhibition suppresses neuroblastoma proliferation via MYCN destabilization

    Yuki Endo, Ryuichi P. Sugino, Hisanori Takenobu, Kyosuke Mukae, Ryu Okada, Yoshitaka Shinno, Masayuki Haruta, Shunpei Satoh, Jesmin Akter, Naoko Hattori, Atsuko Nakazawa, Toshikazu Ushijima, Akira Nakagawara, Miki Ohira, Masaki Nio, Takehiko Kamijo

    BMC Cancer     2025.11

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1186/s12885-025-14882-7

  2. Noncanonical PRC1.1 targets BTG2 to retain cyclin gene expression and cell growth in neuroblastoma

    Shunpei Satoh, Mariko Hasegawa, Ryu Okada, Masayuki Haruta, Hisanori Takenobu, Miki Ohira, Takehiko Kamijo

    Oncogenesis     2025.6

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/s41389-025-00561-6

  3. Photoinduced Actin Aggregation Involves Cell Death: A Mechanism of Cancer Cell Cytotoxicity after Near-Infrared Photoimmunotherapy

    Kazuhide Sato, Tomoko Okada, Ryu Okada, Hirotoshi Yasui, Mizuki Yamada, Yoshitaka Isobe, Yuko Nishinaga, Misae Shimizu, Chiaki Koike, Rika Fukushima, Kazuomi Takahashi, Shunichi Taki, Ayako Kato, Mitsuo Sato, Toshihiko Ogura

    ACS Nano     2025.3

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1021/acsnano.5c00104

  4. L3MBTL2 maintains <i>MYCN</i>‐amplified neuroblastoma cell proliferation through silencing <i>NRIP3</i> and <i>BRME1</i> genes

    Ryu Okada, Hisanori Takenobu, Shunpei Satoh, Ryuichi P. Sugino, Ritsuko Onuki, Masayuki Haruta, Kyosuke Mukae, Atsuko Nakazawa, Jesmin Akter, Miki Ohira, Takehiko Kamijo

    Genes to Cells     2024.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    <jats:title>Abstract</jats:title><jats:p>Epigenetic alterations critically affect tumor development. Polycomb‐group complexes constitute an evolutionarily conserved epigenetic machinery that regulates stem cell fate and development. They are implicated in tumorigenesis, primarily via histone modification. Polycomb repressive complex 1 (PRC1) complexes 1–6 (PRC1.1–6) mediate the ubiquitination of histone H2A on lysine 119 (H2AK119ub). Here, we studied the functional roles of a PRC1.6 molecule, L3MBTL2, in neuroblastoma (NB) cells. <jats:italic>L3MBTL2</jats:italic>‐knockout and knockdown revealed that L3MBTL2 depletion suppressed NB cell proliferation via cell‐cycle arrest and gamma‐H2A.X upregulation. <jats:italic>L3MBTL2‐</jats:italic>knockout profoundly suppressed xenograft tumor formation. Transcriptome analysis revealed suppressed cell‐cycle‐related and activated differentiation‐related pathways. <jats:italic>Break repair meiotic recombinase recruitment factor 1</jats:italic> (<jats:italic>BRME1</jats:italic>) and <jats:italic>nuclear receptor interacting protein 3</jats:italic> (<jats:italic>NRIP3</jats:italic>) were notably de‐repressed by <jats:italic>L3MBTL2</jats:italic>‐knockout. The deletion of <jats:italic>L3MBTL2</jats:italic> reduced enrichment of H2AK119ub and PCGF6 at transcriptional start site proximal regions of the targets. Add‐back studies unveiled the importance of L3MBTL2‐BRME1 and ‐NRIP3 axes for NB cell proliferation. We further manifested the association of MYCN with de‐repression of <jats:italic>NRIP3</jats:italic> in an <jats:italic>L3MBTL2</jats:italic>‐deficient context. Therefore, this study first revealed the significance of <jats:italic>L3MBTL2‐</jats:italic>mediated gene silencing in MYCN‐amplified NB cells.</jats:p>

    DOI： 10.1111/gtc.13148

  5. ATM depletion induces proteasomal degradation of FANCD2 and sensitizes neuroblastoma cells to PARP inhibitors Open Access

    Sultana Parvin, Jesmin Akter, Hisanori Takenobu, Yutaka Katai, Shunpei Satoh, Ryu Okada, Masayuki Haruta, Kyosuke Mukae, Tomoko Wada, Miki Ohira, Kiyohiro Ando, Takehiko Kamijo

    BMC Cancer     2023.4

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    Language：English   Publishing type：Research paper (scientific journal)  

    <jats:title>Abstract</jats:title><jats:sec>
    <jats:title>Background</jats:title>
    <jats:p>Genomic alterations, including loss of function in chromosome band 11q22-23, are frequently observed in neuroblastoma, which is the most common extracranial childhood tumour. In neuroblastoma, <jats:italic>ATM</jats:italic>, a DNA damage response-associated gene located on 11q22-23, has been linked to tumorigenicity. Genetic changes in <jats:italic>ATM</jats:italic> are heterozygous in most tumours. However, it is unclear how ATM is associated with tumorigenesis and cancer aggressiveness.</jats:p>
    </jats:sec><jats:sec>
    <jats:title>Methods</jats:title>
    <jats:p>To elucidate its molecular mechanism of action, we established <jats:italic>ATM</jats:italic>-inactivated NGP and CHP-134 neuroblastoma cell lines using CRISPR/Cas9 genome editing. The knock out cells were rigorously characterized by analyzing proliferation, colony forming abilities and responses to PARP inhibitor (Olaparib). Western blot analyses were performed to detect different protein expression related to DNA repair pathway. ShRNA lentiviral vectors were used to knockdown ATM expression in SK-N-AS and SK-N-SH neuroblastoma cell lines. <jats:italic>ATM</jats:italic> knock out cells were stably transfected with FANCD2 expression plasmid to over-expressed the FANCD2. Moreover, knock out cells were treated with proteasome inhibitor MG132 to determine the protein stability of FANCD2. FANCD2, RAD51 and γH2AX protein expressions were determined by Immunofluorescence microscopy.</jats:p>
    </jats:sec><jats:sec>
    <jats:title>Results</jats:title>
    <jats:p>Haploinsufficient <jats:italic>ATM</jats:italic> resulted in increased proliferation (<jats:italic>p</jats:italic> &lt; 0.01) and cell survival following PARP inhibitor (olaparib) treatment. However, complete <jats:italic>ATM</jats:italic> knockout decreased proliferation (<jats:italic>p</jats:italic> &lt; 0.01) and promoted cell susceptibility to olaparib (<jats:italic>p</jats:italic> &lt; 0.01). Complete loss of ATM suppressed the expression of DNA repair-associated molecules FANCD2 and RAD51 and induced DNA damage in neuroblastoma cells. A marked downregulation of FANCD2 expression was also observed in shRNA-mediated ATM-knockdown neuroblastoma cells. Inhibitor experiments demonstrated that the degradation of FANCD2 was regulated at the protein level through the ubiquitin–proteasome pathway. Reintroduction of FANCD2 expression is sufficient to reverse decreased proliferation mediated by ATM depletion.</jats:p>
    </jats:sec><jats:sec>
    <jats:title>Conclusions</jats:title>
    <jats:p>Our study revealed the molecular mechanism underlying <jats:italic>ATM</jats:italic> heterozygosity in neuroblastomas and elucidated that <jats:italic>ATM</jats:italic> inactivation enhances the susceptibility of neuroblastoma cells to olaparib treatment. These findings might be useful in the treatment of high-risk NB patients showing <jats:italic>ATM</jats:italic> zygosity and aggressive cancer progression in future.</jats:p>
    </jats:sec>

    DOI： 10.1186/s12885-023-10772-y

    Open Access

  6. Polycomb group protein BMI1 protects neuroblastoma cells against DNA damage-induced apoptotic cell death Open Access

    Nobuhiro Akita, Ryu Okada, Kyosuke Mukae, Ryuichi P. Sugino, Hisanori Takenobu, Koji Chikaraishi, Hidemasa Ochiai, Yohko Yamaguchi, Miki Ohira, Haruhiko Koseki, Takehiko Kamijo

    Experimental Cell Research     2023.1

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    Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.yexcr.2022.113412

    Open Access

  7. Polycomb <scp>EZH1</scp> regulates cell cycle/5‐fluorouracil sensitivity of neuroblastoma cells in concert with <i>MYCN</i> Open Access

    Yoshitaka Shinno, Hisanori Takenobu, Ryuichi P. Sugino, Yuki Endo, Ryu Okada, Masayuki Haruta, Shunpei Satoh, Kyosuke Mukae, Dilibaerguli Shaliman, Tomoko Wada, Jesmin Akter, Kiyohiro Ando, Atsuko Nakazawa, Hideo Yoshida, Miki Ohira, Tomoro Hishiki, Takehiko Kamijo

    Cancer Science     2022.12

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    Language：English   Publishing type：Research paper (scientific journal)  

    <jats:title>Abstract</jats:title><jats:p>In the present study, we found that EZH1 depletion in <jats:italic>MYCN</jats:italic>‐amplified neuroblastoma cells resulted in significant cell death as well as xenograft inhibition. EZH1 depletion decreased the level of H3K27me1; the interaction and protein stabilization of MYCN and EZH1 appear to play roles in epigenetic transcriptional regulation. Transcriptome analysis of EZH1‐depleted cells resulted in downregulation of the cell cycle progression‐related pathway. In particular, Gene Set Enrichment Analysis revealed downregulation of reactome E2F‐mediated regulation of DNA replication along with key genes of this process, <jats:italic>TYMS</jats:italic>, <jats:italic>POLA2</jats:italic>, and <jats:italic>CCNA1</jats:italic>. <jats:italic>TYMS</jats:italic> and <jats:italic>POLA2</jats:italic> were transcriptionally activated by MYCN and EZH1‐related epigenetic modification. Treatment with the EZH1/2 inhibitor UNC1999 also induced cell death, decreased H3K27 methylation, and reduced the levels of <jats:italic>TYMS</jats:italic> in neuroblastoma cells. Previous reports indicated neuroblastoma cells are resistant to 5‐fluorouracil (5‐FU) and TYMS (encoding thymidylate synthetase) has been considered the primary site of action for folate analogues. Intriguingly, UNC1999 treatment significantly sensitized MYCN‐amplified neuroblastoma cells to 5‐FU treatment, suggesting that EZH inhibition could be an effective strategy for development of a new epigenetic treatment for neuroblastoma.</jats:p>

    DOI： 10.1111/cas.15555

    Open Access

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