Elucidation of cancer progression through dysfunction of ubiquitin system

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10513
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Nara Medical University
• Principal Investigator: Migita Kazuhiro 奈良県立医科大学, 医学部, 研究員 (40570990)
• Research Collaborator: Obara Shinsaku
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 胃癌 / E3ユビキチンリガーゼ

Outline of Final Research Achievements

We investigated the roles of Ring finger protein 126 (RNF126) in the progression of gastric cancer. In the immunohistochemical analyses, the RNF126 expression level was significantly associated with the tumor depth. The patients with a RNF126-high tumor had a significantly lower overall survival rate than the patients with a RNF126-low tumor. Multivariate analysis identified the RNF126 status as an independent prognostic factor. We further investigated the roles of RNF126 in vitro using a small interfering RNA (siRNA). RNF126 gene silencing significantly inhibited the proliferation of human gastric cancer cells, MKN45 and MKN74, through the cell cycle arrest. Furthermore, RNF126 gene silencing improved the sensitivity to 5-FU. Our findings indicate that RNF126 might play an important role in regulating the proliferation and chemo-resistance of gastric cancer cells.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

本研究はユビキチンシステムにおいて中心的役割を担うE3ユビキチンリガーゼに着目し、胃癌進展におけるその異常の意義・役割を検討した。E3ユビキチンリガーゼであるRNF126はヒト胃癌組織で過剰発現しており、その発現レベルは腫瘍進達度と関連し、独立した予後規定因子となるなど臨床的意義を有することが判明した。また、発現レベルは胃癌細胞の増殖能、抗癌剤への感受性に関連することが明らかとなり、RNF126は胃癌の増殖、治療抵抗性に深く関与することが示唆された。本研究の成果はユビキチンシステム異常を介した消化器癌進展の解明、新たな癌治療開発の礎となるものと考えられる。