A mechanism and novel targeted therapy for EPPK1 in non-small cell lung cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17231
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Arimura Ken 東京女子医科大学, 医学部, 講師 (60771269)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: EPPK1 / CRISPR-Cas9 / MYC/p53 pathway

Outline of Final Research Achievements

EPPK1 expression is associated with smoking and poor prognosis in early-stage lung cancer. We used CRISPR-Cas9 to knockout of EPPK1 and observed that cancer cells underwent a transition from a mesenchymal to epithelial state, leading to decreased cell proliferation and invasion. Furthermore, RNA seq showed that the knockout of EPPK1 caused the downregulation of 11 oncogenes, and the upregulation of 8 tumor suppressor genes. We also observed downregulation of MYC and upregulation of p53 expressions at both the protein and RNA levels after the knockout of EPPK1. Similarly, gene ontology enrichment analysis of molecular function revealed that EPPK1 mRNA was associated with the function of the regulation of mesenchymal cell proliferation, mesenchymal differentiation, and cell growth. Our findings suggest that EPPK1 is associated with smoking and plays a role in regulating cancer progression and tumorigenesis. Therefore, EPPK1 is a potential therapeutic target for lung adenocarcinoma.

Free Research Field

胸部腫瘍

Academic Significance and Societal Importance of the Research Achievements

非小細胞肺がん、特に肺腺がんにおけるEPPK1が果たす病態解明を明らかにした。また、喫煙とtumorigenesisに関連している可能性を示した。このため、肺腺がんにおいてEPPK1標的とした治療法開発につながるため社会的意義のある研究であった。