Mechanisms of cancer malignant transformation created by Regnase-1.

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15504
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Tohoku University
• Principal Investigator: Keito Okazaki 東北大学, 加齢医学研究所, 助教 (70826289)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: Regnase-1 / 腫瘍幹細胞性

Outline of Final Research Achievements

The function of Regnase-1 in non-small cell lung cancers (NSCLCs) remains to be unclear. To solve that problem, I generated Regnase-1 knockout cells, and demonstrated that Regnase-1 contributes to tumor stem-like phenotype in NSCLCs through RNA sequencing analysis, evaluation of oncosphere-formation, and xenograft and serial transplantation. In addition, by performing transient knockdown (KD) experiments of Regnase-1 in 15 different NSCLC cell lines, I demonstrated that the concept is universal. Finally, I performed drug-induced KD experiments of Regnase-1, which showed that inhibition of Regnase-1 function also suppresses tumor growth.

Free Research Field

癌研究

Academic Significance and Societal Importance of the Research Achievements

本研究から、Regnase-１はNSCLCsにおいて、普遍的を以て腫瘍幹細胞性の維持を支えていることが証明された。このことは、特に、有望な治療標的の探索に難渋している扁平上皮がんや大細胞がんにおいて臨床的的価値が高いと考えられる。また、CD8(+)T細胞でRegnase-1を抑制すると抗腫瘍免疫が増強することが報告されていることから、Regnase-1の阻害はがん細胞、がん微小環境両者に有効な治療と考えられ、今後Regnase-1阻害剤の獲得が期待される。