マイクロＲＮＡによるがん幹細胞抑制のメカニズム解明とがん根治を目指した治療応用

阐明microRNA抑制癌症干细胞的机制以及旨在根除癌症的治疗应用

• 批准号: 19J13933
• 负责人: 山本 佑樹
• 金额: $ 1.34万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2019
• 资助国家: 日本
• 起止时间: 2019-04-25 至 2021-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-19J13933/
• 关键词: miRNA; 細胞老化; がん幹細胞

我々は、細胞老化を誘導する マイクロRNA (Senescence-Associated microRNA; SA-miRNA) をがん治療に応用することを目指し研究を行なっている。これまでの研究において、がん細胞の増殖を強く抑制する SA-miRNA を多数同定している。本研究では、がんの悪性化や再発に大きく寄与する、がん幹細胞に対しても増殖抑制効果を示す SA-miRNA を見出すとともに、がん幹細胞の増殖抑制メカニズムについて明らかとすることを目的とした。今回、非常に強いがん増殖抑制効果を示す SA-mIRNA である miR-3140-3p に着目して研究を行った。 本研究により、この miRNA は、がん細胞増殖はもちろんのこと、がん幹細胞性の高いがん細胞株や抗癌剤に耐性を示すがん細胞株にも増殖抑制効果を示すことを明らかとした。また、細胞老化およびがん細胞の増殖抑制メカニズムを明らかとするため、マイクロアレイ解析および in silico 解析を用いて、標的遺伝子候補を絞り込んだ。絞り込んだ標的遺伝子候補に対する siRNA ライブラリーを構築し、正常細胞に対して細胞老化の表現系および細胞老化マーカーを評価するスクリーニングを、がん細胞株に対して細胞の生存率を評価するスクリーニングを行った。その結果、細胞老化およびがん細胞の増殖抑制効果に寄与する遺伝子として SLC7A11 を見出した。さらに、ルシフェラーゼレポーターアッセイにより、miR-3140-3p が SLC7A11 を直接標的としていることも明らかとした。

The cell aging mechanism is used to guide the treatment of RNA (Senescence-Associated microRNA; SA-miRNA). The target is to study the disease. In the study of SA-miRNA, most of them were the same as those in the same group. In this study, the results showed that SA-miRNA cells were infected, the colonization inhibition was induced, the colonization inhibition was induced, and the colonization inhibition was detected. This time, very strong colonization inhibition results show that the results show that the SA-mIRNA is focused on the study of miR-3140-3p. In this study, cell colonization, miRNA, cytopathic acid, cytopathic acid, anti-cancer cell line, anti-cancer tolerance, cell line colonization inhibition and cell growth inhibition were studied in this study. Cell aging, cell aging, cell proliferation inhibition, cell proliferation, cell aging, cell proliferation, cell aging, cell aging, cell proliferation, cell proliferation, cell aging, cell aging, cell proliferation, colony inhibition, cell proliferation, cell aging, cell aging, cell proliferation, cell proliferation, cell aging, cell aging, cell proliferation, colony inhibition, cell proliferation, cell aging, cell aging, cell proliferation, cell proliferation, cell aging, cell aging, cell proliferation, colony inhibition, cell proliferation, cell aging, cell aging, cell growth inhibition, cell proliferation, cell aging, cell aging, cell proliferation, colony inhibition, cell proliferation, cell aging, cell aging, cell proliferation, The children of this disease were infected by siRNA cells, normal cells, aging cells, aging cells, cell lines, cell survival rate, cell line survival rate, cell survival rate, cell survival rate, The results showed that the results of cell aging and the inhibition of cell colonization were related to the results of cell aging, cell aging and cell proliferation inhibition. The results were compared with the results of cell aging, cell aging and cell proliferation inhibition. The results were compared with the results of cell aging, cell aging and cell proliferation inhibition. The results were compared with the results of cell aging, cell aging and cell proliferation inhibition. The results were compared with the results of cell aging, cell aging and cell proliferation inhibition. The results were compared with the results of cell aging and SLC7A11. MiR-3140-3p, SLC7A11, direct, etc.

项目成果

A high-content cellular senescence screening identifies a novel tumor suppressive microRNA

高内涵细胞衰老筛查鉴定出一种新型肿瘤抑制性 microRNA

• 发表时间: 2019
• 作者: Yuki Yamamoto;Ayaka Nishiura;Kimiyoshi Yano;Saori Fukunaga;Masaki Kinehara;Ryou-u Takahashi;Hidetoshi Tahara
• 通讯作者: Hidetoshi Tahara