p53 family target ncRNAs and gastrointestinal tumorigenesis

2017 Fiscal Year Final Research Report

• Project/Area Number: 26460944
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Sapporo Medical University
• Principal Investigator: Yasushi Sasaki 札幌医科大学, 医療人育成センター, 教授 (70322328)
• Co-Investigator(Renkei-kenkyūsha): MARUYAMA Reo 公益財団法人がん研究会, がん研究所, 研究員 (60607985)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: 消化器癌 / p53 / p73 / p63 / ncRNA / 標的遺伝子

Outline of Final Research Achievements

Recent studies revealed that p53 family proteins are important for the regulation of cell invasion and migration. Microarray analysis showed that breast cancer metastasis-suppressor 1- like (BRMS1L) is upregulated by p53 family proteins, specifically p53, TAp63γ, and TAp73β. We identified two responsive elements of p53 family proteins in the first intron and upstream of BRMS1L. These response elements are well conserved among mammals. Functional analysis showed that ectopic expression of BRMS1L inhibited cancer cell invasion and migration; knockdown of BRMS1L by siRNA induced the opposite effect. Importantly, clinical databases revealed that reduced BRMS1L expression correlated with poor prognosis in patients with breast and brain cancer. Altogether, these results strongly indicate that BRMS1L is one of the mediators downstream of the p53 pathway, and inhibits cancer cell invasion and migration, which are essential steps in cancer metastasis.

Free Research Field

消化器内科学