Functional significance of the RHOA mutation in gastric cancer

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10518
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Serizawa Akiko 東京女子医科大学, 医学部, 助教 (70408491)
• Co-Investigator(Kenkyū-buntansha): 古川 徹 東北大学, 医学系研究科, 教授 (30282122)
• Research Collaborator: Yamamoto Masakazu
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: RHOA / 消化管腫瘍 / 増殖抑制 / 3次元スフェロイド培養 / RNA干渉

Outline of Final Research Achievements

We determined genotypes of RHOA in 11 gastrointestinal cancer cell lines. Attenuated proliferation was observed both in RHOA knockdown cells with RHOA mutation and in those without RHOA mutation, and vice versa. However, through transcriptome analyses, we revealed that downregulation of lnc-DERA-1 was common after the RHOA knockdown in the RHOA-mutated cell lines. We also found that the genes associated with metabolism of small molecules and oxidation-reduction process were commonly downregulated in cells whose proliferation was attenuated by the knockdown of RHOA. These results suggest that knockdown of RHOA may induce metabolic stress by downregulating the essential cellular metabolic molecules and attenuation of cellular proliferation.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

本研究によって、RHOA・変異RHOAの機能が消化管腫瘍のtumorigenicityに与える影響が明らかとなり、治療標的の候補となり得る経路・下流遺伝子の情報を網羅的な解析の中より得ることができた。このことは、今後消化管腫瘍のRHOA機能に関連する分子標的治療のstrategyを決定する上で不可欠と考えられる。