Mechanisms for the establishment of serum miRNA profiles through inter-cellular communication.

2021 Fiscal Year Final Research Report

• Project/Area Number: 18H02703
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: National Cancer Center Japan
• Principal Investigator: Tsuchiya Naoto 国立研究開発法人国立がん研究センター, 研究所, ユニット長 (30322712)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: miRNA / 細胞外分泌 / 細胞内ネットワーク

Outline of Final Research Achievements

To understand the overall functions of the miRNA system for the establishment of malignant cells and tissues, we analyzed the source of extracellular miRNAs (exmiRNA), being detectable in the serum samples from cancer patients. Interestingly, cancer cell-derived exmiRNAs did not contribute to establishing serum miRNA profiles. Therefore, the serum miRNA profile mirrors the reactive changes of patients with cancer-bearing conditions. In addition, the biological relevance of miRNA structural isoforms, which are frequently detectable in serum of the cancer patients, was also investigated. Interestingly, the dominancy for the expression of miRNA isoforms clearly correlated with malignant properties of lung cancers. By detailed analyses, we demonstrated that miRNA structural isoforms expression reflects the activation of the cellular miRNA regulatory network, which is controlled by several RNA binding proteins and is required for the establishment of oncogenic gene expression profiles.

Free Research Field

分子細胞生物学、腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

miRNAは、がん医療創出の有望なツールとして研究されているが、発がんにおける生物学的な意義の全容は理解されていない。細胞外へと分泌されるmiRNAの意義や機能、血清miRNAプロファイルの成立に貢献する分泌細胞も特定されていない。本研究では、血清miRNAプロファイルの成立にがん細胞由来の分泌miRNAがほとんど関与しないこと、正常組織由来と考えられるmiRNAの貢献が大きいことを見出した。さらに、構造アイソフォームの発現優位性がoncogenicなmiRNA制御ネットワークの活性化を反映することも明らかにした。本成果は、miRNAの実用化に向けて、極めて有用な知見を提示する。