Updated on 2024/12/20

写真a

 
ITO Sachio
 
Organization
Faculty of Medicine, Dentistry and Pharmaceutical Sciences Assistant Professor
Position
Assistant Professor
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Degree

  • 修士(農学) ( 岡山大学 )

  • Ph.D in Medicine ( Okayama University )

Research Interests

  • 分子生物学

  • 分子腫瘍学

  • Molecular Biology

  • Molecular Oncology

  • Molecular Cytogenetics

Research Areas

  • Life Science / Molecular biology

  • Life Science / Cell biology

  • Life Science / Medical biochemistry

  • Life Science / Pathological biochemistry

Education

  • Okayama University   医学研究科   病理系病態遺伝子解析

    - 2001

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    Country: Japan

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  • Okayama University    

    - 2001

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  • Okayama University of Science    

    - 1993

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  • Okayama University of Science   理学部   生物化学科

    - 1993

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    Country: Japan

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Research History

  • 岡山大学学術研究院医歯薬学域   助教

    2021

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  • - 岡山大学医歯薬学総合研究科 助教

    2004

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  • - Assistant Professor,Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,Okayama University

    2004

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Professional Memberships

 

Papers

  • Human NINEIN polymorphism at codon 1111 is associated with the risk of colorectal cancer. Reviewed International journal

    Yukiko Yasuda, Akiko Sakai, Sachio Ito, Kaori Sasai, Akisada Ishizaki, Yoshiya Okano, Seito Kawahara, Yoshimi Jitsumori, Hiromasa Yamamoto, Nagahide Matsubara, Kenji Shimizu, Hiroshi Katayama

    Biomedical reports   13 ( 5 )   45 - 45   2020.11

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    Publishing type:Research paper (scientific journal)  

    NINEIN serves an essential role in centrosome function as a microtubule organizing center, and in the reformation of the interphase centrosome architecture following mitosis. In the present study, the association between NINEIN Pro1111Ala (rs2236316), a missense single nucleotide polymorphism, and the risk of colorectal cancer (CRC), related to smoking and alcohol consumption habits in 200 patients with CRC and 1,141 cancer-free control participants were assessed in a case-control study performed in Japan. The results showed that the NINEIN Ala/Ala genotype compared with the Pro/Pro genotype was significantly more associated with an increased risk of CRC, and the males with the Ala/Ala genotype exhibited a significantly increased risk of CRC compared with those with Pro/Pro and Pro/Ala genotypes. Stratified analyses of the Ala/Ala genotype with CRC risk further showed an increased association in never/light drinkers (<23 g of ethanol/day), in male never/light drinkers and in male patients with rectal cancer. These findings suggest that the genetic variant of the NINEIN Pro1111Ala polymorphism has a significant effect on CRC susceptibility in the Japanese population.

    DOI: 10.3892/br.2020.1352

    PubMed

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  • Decreased miR-200b-3p in cancer cells leads to angiogenesis in HCC by enhancing endothelial ERG expression. Reviewed International journal

    Aye Moh-Moh-Aung, Masayoshi Fujisawa, Sachio Ito, Hiroshi Katayama, Toshiaki Ohara, Yoko Ota, Teizo Yoshimura, Akihiro Matsukawa

    Scientific reports   10 ( 1 )   10418 - 10418   2020.6

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

    Transcription factor ERG (erythroblast transformation-specific (ETS)-related gene) is essential in endothelial differentiation and angiogenesis, in which microRNA (miR)-200b-3p targeting site is expected by miRNA target prediction database. miR-200b is known decreased in hepatocellular carcinoma (HCC), however, the functional relation between ERG and miR-200b-3p, originating from pre-miR-200b, in HCC angiogenesis remains unclear. We investigated whether hepatocyte-derived miR-200b-3p governs angiogenesis in HCC by targeting endothelial ERG. Levels of miR-200b-3p in HCC tissues were significantly lower than those in adjacent non-HCC tissues. Poorly differentiated HCC cell line expressed lower level of miR-200b-3p compared to well-differentiated HCC cell lines. The numbers of ERG-positive endothelial cells were higher in HCC tissues than in adjacent non-HCC tissues. There was a negative correlation between the number of ERG-positive cells and miR-200b-3p expression in HCC tissues. Culture supernatants of HCC cell lines with miR-200b-3p-overexpression reduced cell migration, proliferation and tube forming capacity in endothelial cells relative to the control, while those with miR-200b-3p-inhibition augmented the responses. Exosomes isolated from HCC culture supernatants with miR-200b-3p overexpression suppressed endothelial ERG expression. These results suggest that exosomal miR-200b-3p from hepatocytes suppresses endothelial ERG expression, and decreased miR-200b-3p in cancer cells promotes angiogenesis in HCC tissues by enhancing endothelial ERG expression.

    DOI: 10.1038/s41598-020-67425-4

    PubMed

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  • Human RAD 17 Polymorphism at Codon 546 Is Associated with the Risk of Colorectal Cancer Reviewed

    Yukiko Yasuda, Akiko Sakai, Sachio Ito, Kaori Sasai, Hiromasa Yamamoto, Nagahide Matsubara, Mamoru Ouchida, Hiroshi Katayama, Kenji Shimizu

    ACTA MEDICA OKAYAMA   71 ( 1 )   59 - 68   2017.2

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:OKAYAMA UNIV MED SCHOOL  

    Human RAD17 acts as an activator of checkpoint signals in response to DNA damage. Here we evaluated the association of hRAD17 Leu546Arg (rs1045051), a missense single nucleotide polymorphism, with the risk of colorectal cancer (CRC) in relation to smoking and alcohol consumption habits in 212 CRC patients and 1,142 cancer-free controls in a case-control study conducted in Japan. The results showed that the hRAD17 Leu/Arg genotype compared to the Leu/Leu genotypes was significantly associated with the protective effect on CRC risk with the adjusted odds ratio (OR) of 0.68 [95% confidence interval (CI): 0.49-0.95, p=0.024], and the males with the Arg/Arg genotype had a greater risk of CRC compared to those with the Leu/Leu and Leu/Arg genotypes (OR=1.87, 95% CI 1.03-3.40, p=0.04). In stratified studies, the protective effect of the Leu/Arg genotype on CRC risk was markedly higher in the light smokers (&lt; 20 pack years) (OR=0.61, 95% CI 0.40-0.94, p=0.024) and the rectal cancer patients (OR=0.49, 95% CI 0.31-0.78, p=0.003). The risk of the Arg/Arg genotype was associated with heavy smoking (&gt;= 20 pack-years) (OR=2.24, 95% CI 1.09-4.61, p=0.03). These findings suggest that the genetic variant of hRAD17 Leu546Arg polymorphism has a significant effect on CRC susceptibility in Japanese.

    Web of Science

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  • Unique circulating microRNAs in relation to EGFR mutation status in Japanese smoker male with lung adenocarcinoma Reviewed

    Sachio Ito, Yoshihiro Kamoto, Akiko Sakai, Kaori Sasai, Tatsuro Hayashi, Shinichi Toyooka, Hiroshi Katayama

    Oncotarget   8 ( 70 )   114685 - 114697   2017

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Impact Journals LLC  

    The incidence of lung adenocarcinoma has been increasing recently in smokers. The molecular target therapy has been developed for lung adenocarcinoma patients harboring EGFR gene mutation. However, the treatment modalities for patients without mutation are currently limited. Thus, analysis of EGFR gene mutation status at early stage is important strategy to classify the patients for improving treatments and prognosis efficiently. This study aimed to identify microRNA (miRNA) signature in relation to mutation status in EGFR gene in early stage of lung adenocarcinoma male patients with smoking history. MiRNA profiles were assessed by microarray in paired plasma and tissue pooled from 10 EGFR wild type (EGFR-wt) and 10 EGFR mutated (EGFR-mut) patients. Expressions of selected miRNAs were verified further by real-time qRT-PCR in 83 plasma samples consisting of 55 EGFR-wt patients and 28 EGFR-mut patients and their correlation with clinicopathological parameters and EGFR gene mutation status were evaluated. We found that seven miRNAs (miR-16-5p, miR-23a-3p, miR-103a-3p, miR122-5p, miR-223-3p, miR-346 and miR-451a) were differentially expressed in stage I and stage I+II. Especially, miR-23a-3p was only miRNA shown higher expression in EGFR-wt patients than EGFR-mut patients. Thus, our findings could be useful non-invasive biomarkers to differentiate mutation status in EGFR gene in smoker lung adenocarcinoma male patients.

    DOI: 10.18632/oncotarget.21425

    Scopus

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  • Genetic polymorphism at codon 546 of the human RAD17 contributes to the risk for esophageal squamous cell carcinoma. Reviewed International journal

    Yukiko Yasuda, Akiko Sakai, Sachio Ito, Yuichiro Mita, Takayuki Sonoyama, Shunsuke Tanabe, Yasuhiro Shirakawa, Yoshio Naomoto, Hiroshi Katayama, Kenji Shimizu

    International journal of molecular epidemiology and genetics   7 ( 1 )   58 - 66   2016

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

    Human RAD17, a human homolog of the Schizosaccharomyces pombe cell cycle checkpoint gene RAD17, plays a significant role in activating checkpoint signals in response to DNA damage. We evaluated the association of hRAD17 Leu546Arg (rs1045051), a missense single nucleotide polymorphism, with the risk of esophageal squamous cell carcinoma in relation to smoking and alcohol consumption history in 154 esophageal squamous cell carcinoma male patients and 695 cancer-free male controls by a case-control study conducted in Japan. The results showed that the hRAD17 Arg/Arg genotype compared to the Leu/Leu and Leu/Arg genotypes was significantly associated with the risk of the esophageal squamous cell carcinoma with an adjusted odds ratios of 2.22 (95% CI: 1.19-4.16 P=0.013). In stratified studies, the risk of esophageal squamous cell carcinoma was markedly higher in light drinkers (less than 23 g ethanol/day) with the Arg/Arg genotype than in heavy drinkers (excess of 23 g ethanol/day) with the Arg/Arg genotype (OR=2.83, 95% CI: 1.05-7.61, P=0.04). We concluded that the genetic variant of hRAD17 Leu546Arg polymorphism exerts a significant effect on esophageal squamous cell carcinoma risk among Japanese men.

    PubMed

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MISC

  • Spred2 downregulates cancer stemness in HCC cells, targeting on miR-506-3p and its downstream KLF4

    GAO Tong, ITO Sachio, FUJIWARA Masahito, OHARA Toshiaki, YOSHIMURA Teizo, WANG Tianyi, MATSUSHITA Akihiro

    51 - 51   2022

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  • Spred2はHCCで幹細胞性をmiR-506-3pによって一部負に抑制する(Spred2 down-regulates stemness in HCC partly through targeting miR-506-3p)

    高 桐, 藤澤 真義, Aye Moh Moh Aung, 大原 利章, 吉村 禎造, 王 天一, 伊藤 佐智夫, 松川 昭博

    日本病理学会会誌   110 ( 1 )   225 - 225   2021.3

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    Language:English   Publisher:(一社)日本病理学会  

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  • A431細胞の上皮間葉転換におけるマトリックス分解酵素の解析

    大月孝志, 障子友理, 兒玉慎太郎, YAN Wanyu, HATIPOGLU, Omer Faruk, 西村拓人, 立木美穂, 稲垣純子, 伊藤佐智夫, 片山博志, 廣畑聡

    日本分子生物学会年会プログラム・要旨集(Web)   42nd   2019.12

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  • 細胞分裂期制御タンパク質による新規転写調節機構の解明

    笹井香織, TREEKITKARNMONGKOL Warapen, 伊藤佐智夫, MAITY Sankar N, SEN Subrata, 片山博志

    日本分子生物学会年会プログラム・要旨集(Web)   41st   2018.11

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  • 肺癌における癌遺伝子候補MYNNとp53の統合的解析

    伊藤佐智夫, 邱艶艶, 堺明子, 殷佩浩, 片山博志

    日本分子生物学会年会プログラム・要旨集(Web)   41st   2018.11

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Presentations

  • Integrated analysis of oncogene candidate MYNN and p53 in lung cancer

    ITO Sachio

    The 41th Annual Meeting of the Molecular Biology Society of Japan  2018.11 

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    Language:English   Presentation type:Poster presentation  

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  • Unique Circulating MicroRNAs in Relation to EGFR Mutation Status in Japanese Smoker Make with Lung Adenocarcinoma

    ITO Sachio

    The 40th Annual Meeting of the Molecular Biology Society of Japan  2017.12 

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  • 肺癌に関わるmiR-19aの標的遺伝子解析

    第75回日本癌学会学術総会  2016 

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  • Direct targets of miR-19a related to lung cancer

    The 75th Annual Meeting of the Japanese Cancer Association  2016 

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  • 肺癌におけるmiR19a新規標的遺伝子の機能解析

    第38回日本分子生物学会年会  2015 

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Research Projects

  • 転座型がん遺伝子の新規核酸医薬品の探索

    Grant number:23nk0101669h0001  2023.10 - 2025.03

    国立研究開発法人日本医療研究開発機構(AMED)  創薬支援推進事業・創薬総合支援事業 

    大内田守、伊藤佐智夫

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  • 肺がんにおける癌関連遺伝子MYNNとp53の相互制御機構の解明

    Grant number:21K08668  2021.04 - 2024.03

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    伊藤 佐智夫, 堺 明子, 大内田 守

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    Grant amount:\4160000 ( Direct expense: \3200000 、 Indirect expense:\960000 )

    これまでに申請者は、マウス尾静脈接種実験を行い、MYNN過剰発現細胞では肺への癌細胞の浸潤および定着が亢進すること、MYNN発現抑制細胞では浸潤および定着が抑制されることを発見した。またMYNNとp53が直接結合していること、DNA損傷刺激によるp53の活性化でMYNNタンパク質量が減少すること、MYNN過剰発現でp53およびp21が減少すること、MYNN抗体を用いたクロマチン免疫沈降 (ChIP)でMYNNがいくつかのp53標的遺伝子の調節領域に結合することを発見した。
    まずp53によるMYNNの発現調節機構を転写制御および転写後抑制から検証した。p53の過剰発現に伴いMYNN mRNAは僅かながら減少がみられたため、MYNNの調節領域・遺伝子領域に存在するp53レスポンスエレメント (p53RE)を同定し、それらp53REをルシフェラーゼレポータープラスミドにクローニングする。p53-wtをもつA549・H460ヒト肺腺癌細胞に構築したルシフェラーゼレポータープラスミドを導入し、エトポシド等のDNA切断型抗がん剤でp53を活性化させた後、ルシフェラーゼ活性を計測した。その結果では有意差は確認されなかったが引き続き検証を行う。また、p53活性化に伴い発現誘導されるmicroRNA (miRNA)が報告されており、申請者は、これらmiRNAの標的配列をMYNN mRNA-3’UTR上で確認している。p53活性化後、miRNAの発現亢進をTaqMan miRNAアッセイで、MYNNタンパク質発現低下をウェスタンブロット法で検証した。miRNA発現ベクターとMYNN-3’UTRの標的配列(wt/mut)をもつルシフェラーゼレポータープラスミドをそれぞれ構築してルシフェラーゼ活性を計測した。その結果、1つのmiRNAによる転写後抑制が確認された。

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  • CDH17多型とそれに伴うスプライシング変異による短鎖タンパク質の機能解明

    Grant number:20K08308  2020.04 - 2023.03

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    堺 明子, 伊藤 佐智夫, 笹井 香織

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    Grant amount:\4030000 ( Direct expense: \3100000 、 Indirect expense:\930000 )

    カドヘリン17(CDH17)の短鎖型タンパク質は、肝がんの腫瘍部において特異的発現がみられ、患者の生命予後と関連することが報告されている(Wang, XQ et al., Clin. Cancer Res., 2005 and 2006)。肝がんにおけるCDH17の発現はそもそも異所性であることに加え、短鎖型CDH17は、遺伝子内の特定のSNPによってスプライシング変異が誘発され、早期停止コドンが出現することによるものである。膵がんにおいても上記SNPと発症との間に相関がみられることから、我々は、膵がんにおける短鎖型CDH17タンパク質の機能解析解明を試み、1)膵がん細胞におけるRNAおよびタンパク質レベルの発現を確認し、2)膜結合部位の欠損に伴い、短鎖型CDH17が培地中に遊離して分泌型タンパク質として機能しうることを明らかにした。3)作製したオーダーメイド抗体は、期待通り、短鎖型CDH17のみを検出した。4)短鎖型CDH17の発現実験では、明らかながん化促進能はみられなかったことから、5)膵がんではとくに重要である間質細胞の膵星細胞株hPSC-14を入手し、膵がん細胞との共培養条件での短鎖型CDH17の機能評価を試みた。
    以上のように、短鎖型CDH17は、膵がん細胞で発現し、培地中に放出されることにより、膵がん発症のオッズ比を高めると考えられる。同タンパク質の間質細胞への影響を詳細に評価し、当初の目的に沿って、抗体アレイ解析によるシグナル経路の解明を予定していたが、申請者の退職により、本研究は2021年度で廃止となった。

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  • 転写制御破綻によるトリプルネガティブ乳癌発症メカニズムの解明と新規治療標的の探索

    Grant number:18K08596  2018.04 - 2022.03

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    笹井 香織, 伊藤 佐智夫, 片山 博志

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    Grant amount:\4290000 ( Direct expense: \3300000 、 Indirect expense:\990000 )

    トリプルネガティブ乳癌(TNBC)は進行がはやく極めて予後が悪い。しかしながら、明確な治療標的が存在しないため効果的な治療法が確立されていない。代表者は、細胞分裂期に染色体均等分配を調節するオーロラAの過剰発現マウスがTNBC様の癌を発症すること、オーロラAがTNBCの遺伝子発現プロファイル異常の一因である転写因子Xと核内で相互作用することを見出した。本研究では、TNBC特異的な遺伝子発現異常におけるオーロラA / 転写因子Xパスウェイの全貌を明らかにし、TNBCが抱えるトランスレーショナルリサーチの問題克服を目指す。
    オーロラAは転写因子Xをリン酸化することでオーロラAを含む転写因子複合体の安定化を誘導し、標的遺伝子のプロモーター領域に結合することを突き止めた。このことは細胞周期のG 2 / M期進行に関与する遺伝子の発現調節にオーロラAの活性が関与していることを示唆した。転写因子Xの擬似リン酸化変異体発現細胞は、コントロールおよび非リン酸化変異体発現細胞と比較して、G 2 / M期遺伝子の発現増加と細胞増殖速度の増加を示した。より詳細に解析するため、同定した転写因子Xのリン酸化部位を特異的に認識する抗リン酸化抗体の作製を行った。
    また、2種のヒストンアセチル化酵素YとZがオーロラAと結合し、アセチル化依存的なオーロラAの活性化とアセチル化非依存的なタンパク質安定化の両方を促すことを突き止めた。さらに、オーロラAのアセチル化部位の一部を特定し、抗アセチル化特異的抗体の作製を行った。

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  • Role of Aurora kinase in RNA metabolism

    Grant number:17K08762  2017.04 - 2020.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Katayama Hiroshi

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    Grant amount:\4680000 ( Direct expense: \3600000 、 Indirect expense:\1080000 )

    Here, we report for the first time the essential role of Aurora-A-hnRNP interaction in Aurora-B transcriptional regulation. The results can be summarized as follows: (1) hnRNP controlled Aurora-B mRNA decay by direct binding and transactivated Aurora-B promoter by indirectly affecting CHR region in the promoter. (2) Aurora-A phosphorylated hnRNP on at least two serine residues in vivo. (3) Aurora-A phosphorylation of hnRNP upregulated hnRNP’ transactivation activity to Aurora-B promoter. (4) Both hnRNP loss or overexpression overrode Taxol induced spindle checkpoint arrest and resulted in the production of polyploidy cells, resembling to the phenotypes observed by gain or loss of function of Aurora-B. (5) Both hnRNP loss or overexpression enhances cell motility. These results indicate that Aurora-A/hnRNP play an important role in chromosome stability by regulating Aurora-B RNA metabolism and the deregulation of this complex would promote tumorigenesis and metastasis.

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Class subject in charge

  • Molecular Biology (2024academic year) special  - その他

  • Pracice in Molecular Biology (2024academic year) special  - その他

  • Projects: Molecular Genetics (2024academic year) special  - その他

  • Research Projects: Molecular Genetics (2024academic year) special  - その他

  • Research Projects and Practicals: Molecular Genetics I (2024academic year) special  - その他

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Social Activities

  • 朝日医療大学校講義

    Role(s):Lecturer

    2022.10.5

Academic Activities

  • Acta Medica Okayama 論文査読

    Role(s):Peer review

    2023.3.13 - 2023.3.27

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  • Acta Medica Okayama 論文査読

    Role(s):Peer review

    2022.10.12 - 2022.10.24

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    Type:Peer review 

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  • Acta Medica Okayama 論文査読

    Role(s):Peer review

    2022.1.25 - 2022.3.2

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  • Acta Medica Okayama 論文査読

    Role(s):Peer review

    岡山大学  2021.11.24 - 2021.12.8

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