Revealing the function and the molecular network of a novel lncRNA associated with gastric cancer and gastritis

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15220
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Kitajima Hiroshi 札幌医科大学, 医学部, 助教 (90777971)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 胃がん / 長鎖non-coding RNA / ストレス顆粒

Outline of Final Research Achievements

Gastric cancers (GCs) develop through Helicobacter Pylori-induced chronic gastritis. The involvement of long noncoding RNAs (lncRNAs) in inflammation-related carcinogenesis remains unclear. We have identified a lncRNA TM4SF1AS1, which promotes GC cell proliferation and tumor formation. To unravel pathways and molecular networks associated with TM4SF1AS1 in the tumorigenesis, we comprehensively screened a series of TM4SF1AS1-binding proteins. We identified many stress granule-associated molecules and found that TM4SF1AS1 promoted stress granule-like bodyformation in GC cells. Moreover, TM4SF1AS1 inhibited apoptosis mediated by stress-responsive MAPK. It suggested that TM4SF1AS1 might be a lncRNA link between tumorigenesis and stress granule and a potential therapeutic target.

Free Research Field

分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

これまでlncRNA研究において慢性炎症とがんに関わるlncRNAの報告は少なく、 TM4SF1AS1のようにストレス顆粒と発がんを結びつけるlncRNAの報告はない。また、TM4SF1AS1の阻害は胃がんのみならず他のがん細胞においても細胞増殖の抑制効果があることを確認している。TM4SF1AS1のがん遺伝子的機能とその作用機序は、様々ながんに共通する可能性があり、新たながん治療標的分子となりうることが今後期待される。以上より、本研究の成果は学術的にも社会的にも意義は高いものと考える。