Expression and role of volume-activated anion channels in gastric cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09084
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Toma Atsushi 京都府立医科大学, 医学(系)研究科(研究院), 特任講師 (30516191)
• Co-Investigator(Kenkyū-buntansha): 大辻 英吾 京都府立医科大学, 医学(系)研究科(研究院), 教授 (20244600) ; 塩崎 敦 京都府立医科大学, 医学(系)研究科(研究院), 講師 (40568086)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 胃癌

Outline of Final Research Achievements

The depletion of LRRC8A using siRNA decreased cell proliferation and cellular movement, and promoted the induction of apoptosis in human gastric cancer (GC) cells. The microarray analysis showed the up- or down-regulated expression of genes related to the p53 signaling pathway (JNK, p53, p21, Bcl-2, and FAS) in LRRC8A-knockdown cells. An immunohistochemical analysis revealed a correlation between the expression of LRRC8A and the pT status, and multivariate analysis identifed the strong expression of LRRC8A as an independent prognostic factor for 5-year survival in GC patients. Further, the depletion of SLCO2A1 using siRNA decreased cell proliferation, and promoted the induction of apoptosis in human GC cells. The present results indicate that volume-activated anion channels functions as a mediator of and/or biomarker for GC.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

LRRC8Aが胃癌組織において高発現し、そのRNA干渉が癌細胞に抑制効果を示すことを新たに見出した。LRRC8Aのp53 signaling pathwayを介する新たな腫瘍進展制御機構や、予後因子としての意義を明らかにし、バイオマーカーや治療標的としての可能性を示した。また、SLCO2A1のアポトーシス制御機構を解明し、容積活性化アニオンチャネルを標的とした新規治療への応用が期待される。