| Project/Area Number |
17K11375
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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 |
Otorhinolaryngology
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| Research Institution | Chiba University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
関 直彦 千葉大学, 大学院医学研究院, 准教授 (50345013)
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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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 頭頸部扁平上皮癌 / 機能性RNA / マイクロRNA / 発現プロファイル / miR-99a-3p / 癌抑制遺伝子 / 治療抵抗性 / 分子標的薬 / セツキシマブ / 頭頸部癌 / 扁平上皮癌 |
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| Outline of Final Research Achievements |
microRNAs (miRNAs) are a class of functional noncoding RNAs, and aberrant expression of miRNAs is closely related to cancer pathogenesis. One unique feature of miRNAs is that a single miRNA controls the expression of many transcripts. In this study, we focused on both strands of the miR-99a-duplex (miR-99a-5p: the guide strand, and miR-99a-3p: the passenger strand) based on our miRNA signature in HNSCC. Ectopic expression of these miRNAs into cancer cells revealed that both miRNAs significantly blocked cancer cell migration and invasive abilities, suggesting miR-99a-5p and miR-99a-3p acted as antitumor miRNAs in HNSCC cells. Furthermore, we screened miR-99a-3p controlled oncogenes involved in HNSCC pathogenesis. Thirty-two genes were identified as miR-99a-3p-regulated genes, and 10 genes (STAMBP, TIMP4, TMEM14C, CANX, SUV420H1, HSP90B1, PDIA3, MTHFD2, BCAT1, and SLC22A15) significantly predicted 5-year overall survival.
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| Academic Significance and Societal Importance of the Research Achievements |
マイクロRNAは、僅か19塩基～22塩基の1本鎖RNA分子であるが、1種類のマイクロRNAが、極めて多数の蛋白コード遺伝子を制御する事から注目されている。頭頸部扁平上皮癌においても、マイクロRNAの発現異常が、癌の悪性化に深く関与している。本研究では、頭頸部扁平上皮癌において癌抑制機能を有するmiRNA-99a-3pを見出した。更に、その標的分子が、頭頸部扁平上皮癌患者の予後に影響を及ぼしている事を明らかにした。マイクロRNAを起点とした解析手法により、本疾患の分病理学的な理解が深まる事が期待できる。
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