Identification of anti-cancer drug resistance related microRNAs and its role in colorectal tumors

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09329
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Fujita Health University
• Principal Investigator: Nakagawa Yoshihito 藤田医科大学, 医学部, 講師 (60372108)
• Research Collaborator: Akao Yukihiro
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 大腸癌 / microRNA / 抗癌剤 / 薬剤耐性

Outline of Final Research Achievements

We established four types of 5-FU resistant colon cancer cell line in vitro and in vivo. We then analyzed miRNA expression profile by miRNA array in these 4 cell lines, and identified the drug resistance-related miRNAs. We identified possible miRNAs to be involved in 5-FU resistance by miRNA arrays. We then examined the relationship between miR-31, which was most promising among them, and drug resistance. When we exposed high dose of 5-FU to parent or 5-FU resistant cells, the expression levels of miR-31 were raised higher than those of controls. Notably, the expression levels of miR-31 were positively correlated with the grade of clinical stages of colorectal tumors. The protein expression levels of factor inhibiting hypoxia-inducible factor 1 (FHI-1) were downregulated by transfection of mimic miR-31 into DLD-1 cells. This study provides evidence supporting the association of miR-31 with 5-FU drug resistance and clinical stages of colorectal tumors.

Free Research Field

消化器内科、分子生物学

Academic Significance and Societal Importance of the Research Achievements

実臨床では投与開始直後は抗癌剤が良く効いていても耐性が出来て効き目が悪くなり副作用ばかりが目立つことはしばしば観察される。
本研究は薬剤耐性にmicroRNAがどのように関与するかを調べた。この研究成果は抗癌剤の効果が期待できるかどうかの予測や、効きが悪くなったときにもう一度効果が出るようにするための臨床応用が期待できる。