Personalized cancer management based on microRNA biomarkers

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07146
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor diagnostics
• Research Institution: Fukushima Medical University
• Principal Investigator: Ishigame Teruhide 福島県立医科大学, 医学部, 助教 (50583358)
• Co-Investigator(Kenkyū-buntansha): 岡山 洋和 福島県立医科大学, 医学部, 講師 (20583397) ; 竹之下 誠一 福島県立医科大学, 医学部, 教授 (10167489) ; 千田 峻 福島県立医科大学, 医学部, 博士研究員 (40769642)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: マイクロRNA / 消化器癌

Outline of Final Research Achievements

Although this study originally aimed to investigate microRNAs that are specific to the lymph node involvement in gastric cancer, our microRNA screening strategies were not able to identify potential candidates. We then attempted to focus on the identification of microRNAs that regulate an immune checkpoint molecule, programmed cell death ligand 1 (PD-L1), since immunotherapy against the interaction between PD-1/PD-L1 has recently emerged as a promising strategy for gastrointestinal tract cancers. A comprehensive microRNA screening was conducted using The Cancer Genome Atlas (TCGA) dataset combined with microRNA target prediction programs, followed by the analysis of microarray-based mRNA/miRNA expression datasets and formalin-fixed paraffin-embedded (FFPE) samples by immunohistochemistry and qRT-PCR. Here we identified a tumor suppressive microRNA, miR-148a that can negatively regulate PD-L1, via direct binding to 3'UTR of PD-L1 mRNA.

Free Research Field

消化器癌

Academic Significance and Societal Importance of the Research Achievements

マイクロRNAは標的遺伝子機能を制御することで発癌や癌の進展に重要な役割を担うことが知られている。癌診療においては、癌の診断、予後バイオマーカーや治療反応予測因子、さらに薬剤としての有用性が報告されているものもある。本研究で得られたマイクロRNAの機能や臨床的意義の知見が癌におけるマイクロRNAのさらなる理解や個別化医療の糸口へつながることが期待される。