| Project/Area Number |
17K08764
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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 |
Experimental pathology
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| Research Institution | University of Miyazaki |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 膠芽腫 / 浸潤性増殖 / 細胞周囲微少環境 / プロテアーゼ活性調節 / CD24 / MET / SPINT2 / MALAT1 / プロテアーゼ活性制御 / IGFBP2 / 癌 / 遺伝子 / 病理学 / 細胞・組織 / 脳神経疾患 |
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| Outline of Final Research Achievements |
Glioblastoma (GBM) is a malignant neoplasm with the highest frequency and the most miserable prognosis in brain. Novel therapeutic clues and breakthrough are desired. We have performed exploratory and functional analysis for novel genes which are involved in the aggressive features of GBM and focused on CD24, MALAT1, and MET pathway. It was revealed CD24 is involved in proliferation, invasion, and tumorigenicity of GBM. We analyzed cDNA and miRNA profiles in control and CD24 knockdown GBM cells using microarrays to identify downstream factors of CD24. Several genes and miRNA including MALAT1 were identified as candidate progression-associated genes/miRNAs. MALAT1 knockdown using antisense locked nucleic acids resulted in decreased proliferation of glioblastoma cells. Regarding MET, we showed that SPINT2 is epigenetically silenced in most GBM cell lines and about three quarters of GBM tissues and suggested to get involved in prognosis of GBM patients via HGF/MET signaling.
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| Academic Significance and Societal Importance of the Research Achievements |
膠芽腫は、他の癌と比較すると多くはないが、原発性脳実質腫瘍では最も高頻度の悪性腫瘍である。生存期間が2年に満たない、極めて予後の悪い難治性腫瘍であり、新たな治療の糸口やブレークスルーを見出すことはアカデミアの急務である。CD24には、幹細胞性や分化への関与、エクソソームおよび内包する miRNAの質的、量的調節との関連、長鎖非翻訳 RNA である MALAT1には様々なタンパク質や RNA との相互作用による未知の細胞内調節機構への関連、SPINT2 には、（単なる増殖因子の存在ではなく）その活性化機構による細胞周囲微小環境の制御への関与が疑われ、治療に繋がる知見の糸口となることが期待できる。
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