レチノイン酸特異的代謝酵素CYP26のレチノイン酸非依存性がん悪性化機構の解明

阐明视黄酸特异性代谢酶CYP26的非视黄酸依赖性癌症恶变机制

• 批准号: 22K06983
• 负责人: 小野 佑輔
• 金额: $ 2.66万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2022
• 资助国家: 日本
• 起止时间: 2022-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22K06983/
• 关键词: レチノイン酸; ビタミンA; CYP26A1; がん悪性化; 膵癌; 舌癌; トランスクリプトーム

レチノイン酸特異的代謝酵素とされるCytochrome p450 Family 26 Subfamily A Member 1 (CYP26A1)は一部のがん腫で高発現し、がんの悪性化と関わることが報告されている。本研究では、複数の臓器を標的としCYP26A1の臓器横断的ながん悪性化機構の解明を目指している。膵がん、舌扁平上皮がんで外科的切除された症例に対して免疫染色を行い、CYP26A1が高発現する症例があることを明らかとした。また、舌癌では高発現群で有意に予後が悪いことを明らかとした。膵がんにおいては、免疫染色の結果で予後との有意な関連は示されなかったが、TCGAの大規模データセットを用いた解析で、CYP26A1高発現群での有意な予後の悪化が示された。また、CRISPR-Cas9システムを用いて膵がん細胞株、舌がん細胞株いずれにおいてもCYP26A1ノックアウト細胞株を作製した。これらの細胞株ではレチノイン酸投与によって増殖能やコロニー形成能、運動能といったがんの悪性化に関連する機能が低下することが示された。また、本研究ではレチノイン酸特異的代謝酵素とされてきたCYP26A1がレチノイン酸代謝以外の機能を有する可能性について検討することも目的としている。作製したCYP26A1ノックアウト細胞株を用いて、トランスクリプトーム解析、プロテオーム解析を行った結果、レチノイン酸投与によってノックアウト株で大きな遺伝子やタンパク質発現の変化がおこるが、CYP26A1の発現変化自体でも発現する遺伝子やタンパク質のプロファイルが異なることが示された。このことはCYP26A1にレチノイン酸代謝以外の機能があるという仮説を支持するものと考える。

This is a part of Cytochrome P450 Family 26 Subfamily A Member 1 (CYP26A1), which is used as a substitute for sour products. In this study, the mechanism of cross-sectionalization of the CYP26A1 device of the multiplicator is to explain that the target is the target. Surgical excision of flat epithelium of tongue and parenchyma of tongue. Immunostaining was performed and CYP26A1 was used to detect hypertrophy. The patients with cancer of the tongue are interested in the future. The results of immunostaining and immunostaining showed that the results of immunostaining and immunostaining showed that the results of immunostaining and immunostaining showed that the results of immunostaining and immunostaining showed that the results of immunostaining and immunostaining showed that the results of immunostaining and immunostaining showed that the results of immunostaining and immunostaining showed that the results of immunostaining and immunostaining showed that the results of immunostaining and immunostaining showed that the results of immunostaining and immunostaining showed that the results of immunostaining and immunostaining showed that the results of immunostaining and immunostaining showed that the results of immunostaining and immunostaining showed that the results of immunostaining and immunostaining showed that the results of immunostaining and immunostaining showed that the results of immunostaining and immunostaining showed that the results of immunostaining and immunostaining showed that the results of immunostaining and immunostaining showed that the results of immunostaining and immunostaining showed that the results of immunostaining and immunostaining showed that The cell lines of CRISPR-Cas9 and CRISPR-Cas9 were used to make cell lines, tongue cells and tongue cells. The formation and kinetics of cell lines were not affected by the formation of acid and kinetic energy, the formation of energy and kinetic energy. In this study, there is a possibility that there is a possibility of acid substitution in the presence of acid substituted enzymes, such as acid substitutes, CYP26A1 enzymes, acid substitutes, acid substitutes, acid substitutes, In order to improve the quality of the cell line, the results were analyzed, and the results were analyzed in this paper. The results showed that the cell lines were transformed into CYP26A1 cells, and the cells were transformed into autograf. the results were analyzed in detail. In addition to the CYP26A1 technology, there is a significant increase in the number of support devices.

项目成果

Vitamin D metabolism in cancer: potential feasibility of vitamin D metabolism blocking therapy

• DOI: 10.1007/s00795-023-00348-x
• 发表时间: 2023-02
• 期刊: Medical Molecular Morphology
• 影响因子: 1.8
• 作者: Sakura Kamiya;Yuna Nakamori;A. Takasawa;Kumi Takasawa;D. Kyuno;Yusuke Ono;Kazufumi Magara;M. Osanai

レチノイン酸代謝酵素CYP26A1の異常発現は、膵癌細胞の悪性形質の促進に関与する

视黄酸代谢酶CYP26A1的异常表达参与促进胰腺癌细胞的恶性特征

• 发表时间: 2022
• 作者: 井上彩乃;小野佑輔;高澤啓;及能大輔;真柄和史;青山智志;高澤久美;小山内誠
• 通讯作者: 小山内誠

Retinoic acid metabolism in cancer: potential feasibility of retinoic acid metabolism blocking therapy

癌症中的视黄酸代谢：视黄酸代谢阻断疗法的潜在可行性

• DOI: 10.1007/s00795-022-00345-6
• 发表时间: 2023
• 期刊: Medical Molecular Morphology
• 影响因子: 1.8
• 作者: Osanai Makoto;Takasawa Akira;Takasawa Kumi;Kyuno Daisuke;Ono Yusuke;Magara Kazufumi
• 通讯作者: Magara Kazufumi