| Project/Area Number |
16K09592
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Nippon Medical School |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
野呂 林太郎 日本医科大学, 医学部, 講師 (50366738)
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| Research Collaborator |
HAMADA Michiaki
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 肺癌 / 低分子RNA / 薬剤耐性 / 分子標的薬 / ドライバー遺伝子 / トランスレーショナルリサーチ / 薬剤反応性 |
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| Outline of Final Research Achievements |
We tried to identify a long non cording RNA (lncRNA) associated with drug resistance to molecular targeted therapy in lung cancer with driver mutation. We analyzed lnc RNA expression profiles of 4 drug sensitive lung cancer cells and 10 drug reistant lung cancer cells showing cancer stem cell properties and epithelial- mesenchimal trasition using microarray and bioinformatic analysis. We identified CRNDE and IRX5 as lnc RNA and its targeted protein associated with drug resistance to molecular targeted therapy in lung cancer with driver mutation.Inhibition of IRX5 using siRNA showed apototic activity in drug resistant lung cancer cells. CRNDE and IRX5 may be promising targets to overcome the drug resistance to molecular targeted therapy in lung cancer with driver mutation.
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| Academic Significance and Societal Importance of the Research Achievements |
肺癌のEGFR阻害薬やALK阻害薬等の分子標的薬耐性と耐性の根幹となる癌幹細胞・上皮間葉移行の克服は、肺癌薬物療法における大きな課題である。近年長鎖ノンコーディングRNA (lncRNA) に関する発癌への関与が注目され、その全貌の解明が期待されている。今回の研究で、分子標的薬耐性に共通に関与するlncRNAとしてCRNDEを同定し、関連タンパク質がIRX5であり、CRNDEとIRX5は分子標的薬耐性克服に向けた新規治療標的となり得ることを明らかにしたことは社会的意義は大きいと考える。
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