Superenhancer-mediated RUNX3 overexpression in EB virus-associated tumorigenesis

2016 Fiscal Year Final Research Report

• Project/Area Number: 16K14613
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Kumamoto University
• Principal Investigator: Osato Motomi 熊本大学, 国際先端医学研究機構, 特別招聘教授 (90314286)
• Project Period (FY): 2016-04-01 – 2017-03-31
• Keywords: 細胞不死化 / EBウイルス / スーパーエンハンサー

Outline of Final Research Achievements

Epstein-Barr virus (EBV) is well known to be a causative pathogen for widespread types of cancers; however, the molecular basis for its tumorigenesis remains poorly understood. Recent studies by us and others demonstrated that superenhancer (SE)-driven overexpression of the RUNX3 gene may underlie EBV-associated tumorigenesis. To address this question, we first suppressed the SE activity by a SE inhibitor, JQ1. In the presence of JQ1, proliferation of EBV-positive B cell and NKT lymphoma cell lines was all strongly suppressed, due to the suppressed activity of SE and resultant decreased expression of RUNX3. The significance of SE was further confirmed by CRISPR/Cas9 mediated excision of the SE region. In addition, RUNX3 knockdown also led to similar suppression of cell proliferation. These results suggest that SE-driven overexpression of RUNX3 is a key mechanism for EBV-associated tumorigenesis and the inhibition of SE activity by drugs appears to be a novel therapeutic approach.

Free Research Field

総合生物