Mechanism of colorectal tumorigenesis caused by lncRNA-Transcription factor complex

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08299
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: Taniue Kenzui 東京大学, 分子細胞生物学研究所, 助教 (90648627)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: ASBEL / TCF3 / ATF3 / β-catenin / 大腸癌 / 腫瘍形成能 / アンチセンスRNA

Outline of Final Research Achievements

Wnt/β-catenin signaling plays a key role in the tumorigenicity of colon cancer. Furthermore, it has been reported that lncRNAs are dysregulated in several steps of cancer development. Here we show that β-catenin directly activates the transcription of the lncRNA ASBEL (antisense ncRNA in the ANA/BTG3) and the transcription factor TCF3, both of which are required for the survival and tumorigenicity of colorectal cancer cells. ASBEL interacts with and recruits TCF3 to ATF3 locus, where it represses the expression of ATF3. Furthermore, we demonstrate that ASBEL-TCF3-mediated down-regulation of ATF3 expression is required for the proliferation and tumorigenicity of colon tumor cells. Our results reveal a pathway involving an lncRNA and two transcription factors that plays a key role in Wnt/β-catenin-mediated tumorigenesis. Our results suggest that the β-catenin-ASBEL-TCF3-ATF3 pathway may be a promising target for the therapy of colon cancer.

Free Research Field

分子生物学