Elucidation of the control system of intravenous tumor thrombus formation by long-noncoding RNA in hepatocellular carcinoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07608
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Inagaki Yoshinori 東京大学, 医学部附属病院, 助教 (40733390)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 肝細胞癌 / 脈管腫瘍栓 / 長鎖非コードRNA / 浸潤 / 上皮間葉転換

Outline of Final Research Achievements

This study aimed to study the molecular biological roles of long non-coding RNA (lncRNA) in the formation of tumor thrombosis by performing the transcriptomic analysis of hepatocellular carcinoma (HCC) and its tumor thrombosis. The transcriptomic analysis of main HCC tissue and tumor thrombotic tissue from the same patients showed the altered expression of genes and lncRNAs which relate to the cell adhesion and migration. Down-regulation of CRNDE and LINC00665, which showed the elevated expression in tumor thrombotic tissue, induced the suppression of cancer cell invasion in vitro and metastasis in vivo. These results suggested CRNDE and LINC00665 were related to the induction of tumor thrombosis formation and cancer metastasis.

Free Research Field

腫瘍学

Academic Significance and Societal Importance of the Research Achievements

肝細胞癌は現在もなお再発率が高く、脈管での腫瘍栓の形成や転移が患者予後の悪化に大きな影響を及ぼすが、その誘導に関する詳細な分子機構は不明である。外科的切除されることが希少である腫瘍栓組織を用いて網羅的遺伝子発現解析を実施した本研究の成果は、腫瘍栓と主腫瘍との間での遺伝子発現変動を比較した希少な知見として学術的に意義深い。また、長鎖非コードRNAが関与する腫瘍栓形成及び転移の分子機構の解明は、臨床的課題である肝細胞癌の再発の抑止などといった患者予後の改善に寄与する治療法の開発に有効であると期待される。