Identification of novel circular RNA in pancreatic cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03430
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: The University of Tokyo
• Principal Investigator: Otsuka Motoyuki 東京大学, 医学部附属病院, 講師 (90518945)
• Co-Investigator(Kenkyū-buntansha): 丸山 玲緒 公益財団法人がん研究会, がん研究所 がんエピゲノムプロジェクト, プロジェクトリーダー (60607985)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 膵がん

Outline of Final Research Achievements

Circular RNAs (circRNAs) are single-stranded, covalently closed RNA molecules that are produced from pre-mRNAs. Although circRNAs are expressed under specific conditions, their comprehensive expression status is still unclear. Here, we performed a large-scale circRNA profiling analysis in human pancreatic ductal adenocarcinoma (PDAC) tissues. We identified more than 40,000 previously unknown circRNAs, some of which were upregulated in PDAC tissues, compared with normal pancreatic tissues. We determined the full-length sequence of a circRNA upregulated in PDAC, which was derived from two non-coding RNA loci on chromosome 12. The novel circRNA, named circPDAC RNA, was not expressed in normal human cells, but was expressed in PDAC and other carcinoma cells. The circPDAC RNA identified here might serve as a novel biomarker for cancers, including PDAC.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的意義としては、環状RNAに特化したシークエンスによって膵癌という病態時に発現する環状RNAを網羅的に同定できた点が挙げられる。さらにこの環状RNAの全長配列を同定し、非コードＲＮＡエクソンがバックスプライシングで生成されることを明らかにした。さらにこの環状RNAの生物学的機能を解析した。これらの検討は、環状RNAの研究を進めるうえでの基本的な戦略を示したことになる。いっぽう社会的には、この環状RNAが膵癌の新規のバイオマーカーになる可能性があり、臨床的に役立つ可能性が見込まれる。