Comprehensive elucidation of the mechanism of circulating miRNA fluctuations during pancreatic carcinogenesis

2024 Fiscal Year Final Research Report

• Project/Area Number: 23K24188
• Project/Area Number (Other): 22H02927 (2022-2023)
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Multi-year Fund (2024); Single-year Grants (2022-2023)
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Keio University
• Principal Investigator: Matsuzaki Juntaro 慶應義塾大学, 薬学部(芝共立), 准教授 (60464864)
• Co-Investigator(Kenkyū-buntansha): 齋藤 義正 慶應義塾大学, 薬学部(芝共立), 教授 (90360114)
• Project Period (FY): 2024-04-01 – 2025-03-31
• Keywords: 膵臓がん / 細胞外小胞 / マイクロRNA

Outline of Final Research Achievements

For tumors such as pancreatic cancer, where early diagnostic technology is highly anticipated, it is hoped that circulating microRNA (miRNA) diagnosis will become practical. We used CRISPR/Cas9 to perform gene editing on pancreatic progenitor cells established from the primary culture of mouse pancreatic ducts. We created a pancreatic multistage carcinogenesis cell line in which mutations in Kras, Cdkn2a, Tp53, and Smad4 were introduced. Extracellular vesicles were collected from the culture supernatant of each cell line, and miRNA-seq was used to analyze miRNA profiles comprehensively. The cell lines were transplanted into the pancreas of nude mice, and changes in miRNA expression in mouse serum were compared, identifying miRNAs that changed in the blood due to the acquisition of Kras mutations.

Free Research Field

腫瘍診断学

Academic Significance and Societal Importance of the Research Achievements

リキッドバイオプシー技術によるがん早期診断は、その市場規模の成長率がもっとも高い分野のひとつであり、国内外の複数の企業が細胞外miRNA診断研究開発を進めており、本邦から成功させ世界展開へと導く意義は保健福祉的にも経済的にも極めて有益と考えられる。この潮流を下支えする基盤技術として、本研究のような細胞外miRNAの基礎的理解を深める試みは重要である。血中miRNAの生理学的意義の解明は、診断用途としてmiRNAを活用する際に必ず生じるであろう偽陰性・偽陽性を正しく解釈するために臨床上必須であり、また将来的にはこの血中miRNAの機能を標的とした核酸医薬の創出への応用も期待できる。