Novel strategy for colorectal cancer with therapeutic resistance through the dedifferentiation by HOXA5 regulation

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17647
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Osaka University
• Principal Investigator: Hata Tsuyoshi 大阪大学, 医学系研究科, 助教 (80749747)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 大腸癌 / HOXA5 / エピゲノム / 癌幹細胞 / 治療抵抗性

Outline of Final Research Achievements

In order to clarify the significance of HOXA5 expression in colorectal cancer, immunohistological staining was performed using clinical specimens of colorectal cancer. Immunohistochemical staining of about 100 cases, which were operated and collected at our hospital, confirmed that HOXA5 correlates with the favorable prognosis of colorectal cancer patients. In vitro experiment revealed that the HOXA5 expression in the colorectal cancer cell line was increased with DNA methylation inhibitor or HDAC inhibitor, which is partially clinical available as epigenome regulators. Further studies are needed to show whether the regulation of HOXA5 expression level by epigenome regulation can lead to the reduction of malignancy of colorectal cancer.

Free Research Field

大腸癌

Academic Significance and Societal Importance of the Research Achievements

大腸癌におけるHOXA5の発現意義として、HOXA5が大腸癌における独立した予後予測マーカーとなる可能性を明らかにした。また、HOXA5の発現制御メカニズムとしてエピゲノムが関与していることが示唆された。大腸癌の腫瘍悪生度、癌幹細胞や化学療法治療抵抗性との関連性についてさらに解析を進め、今後HOAX5を標的とした大腸癌治療につながる可能性を模索していく。