Comprehensive microRNA expression analysis for castration-resistant prostate cancer and novel therapeutic target molecules

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18087
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Chiba University
• Principal Investigator: Arai Takayuki 千葉大学, 大学院医学研究院, 特任講師 (40793055)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: microRNA / miR-499a-5p / 前立腺癌 / 去勢抵抗性前立腺癌 / NCAPG / CDC6

Outline of Final Research Achievements

Based on our prostate cancer microRNA expression profiles and public gene expression databases, we focused on miR-499a-5p, which was progressively downregulated from non-cancer, untreated prostate cancer, to castration-resistant prostate cancer. We identified NCAPG and CDC6 as the most potent cancer-promoting genes regulating this. These genes, which are deeply involved in the cell cycle, are directly regulated by miR-499a-5p, demonstrating the tumor suppressive function of miR-499a-5p nucleic acid transfection in prostate cancer cell lines. Furthermore, database analysis showed that patients with high expression of these target genes showed more loss of function of p53, suggesting that p53 may play a part in the regulation of microRNA expression.

Free Research Field

マイクロRNA

Academic Significance and Societal Importance of the Research Achievements

本研究の解析対象となるマイクロRNAは、これまで論文報告が殆ど無く、これらマイクロRNAが制御する分子経路の探索は、学術的新規性を有している。また、本研究成果で得られたマイクロRNAや分子は、前立腺癌および去勢抵抗性前立腺癌における新規予後バイオマーカーや新たな治療標的としての可能性を秘めている。我々のこれまでの継続した研究の中で、複数のマイクロRNAの制御を受ける有力な癌遺伝子を見出しており、前立腺癌の分子機構解明に有益な情報を提供できると考える。