Development of therapy for the cancer stem cell by LncRNA

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07196
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor diagnostics
• Research Institution: Osaka University
• Principal Investigator: Otsuka Masahisa 大阪大学, 医学系研究科, 招へい教員 (20597455)
• Co-Investigator(Kenkyū-buntansha): 山本 浩文 大阪大学, 医学系研究科, 教授 (30322184)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 大腸癌 / 幹細胞 / Long non-coding RNA

Outline of Final Research Achievements

To identify the LncRNA related to the cancer stem cells (CSCs), we separated the CSCs and non-CSCs in CRC using the ODC degron system and CSC fraction was augmented. Then, we performed comprehensive gene analysis using CSCs and found that LINC01534 showed high expression in CSCs. Using clinical samples from CRC patients, LINC01534 was associated with poor prognosis in CRC. Functional studies revealed that the LINC01534 knockdown suppressed the cell proliferation and arrested the cell cycle at G2-M phase in CRC cells. Furthermore, we showed that the knockdown of LINC01534 affected the expression of genes related to endoplasmic reticulum (ER) stress and autophagy. Together, we demonstrated the clinical and biological relevance of LINC01534 in association with CSCs, and discovered the effect of LINC01534 on ER stress and autophagy in CRC.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

近年、癌幹細胞は癌治療抵抗性や再発・転移の原因としての関与が報告されており、癌幹細胞を標的とした治療法や新規バイオマーカーの開発が望まれている。本研究の成果は大腸癌幹細胞に特異的なLncRNAであるLINC01534 を見出し、それが癌幹細胞に特異的なメカニズムにも影響していることを突き止めた。本研究で大腸癌幹細胞関連LncRNA としてLINC01534を同定し、大腸癌の再発、転移のバイオマーカーとして、また、新規の治療ターゲットとしての可能性を示すことができた。