Identification of molecular mechanisms leading to treatment resistance in renal cell carcinoma based on functional RNA network analyses

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16723
• 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, 医学部附属病院, 医員 (40793055)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: マイクロRNA / 癌抑制型マイクロRNA / 腎細胞癌 / miR-532-5p / miR-532-3p / AQP9

Outline of Final Research Achievements

Analyses of our previously determined microRNA (miRNA) expression signature of renal cell carcinoma (RCC) and The Cancer Genome Atlas database revealed that both strands of the pre-miR-532-duplex-miR-532-5p (the guide strand) and miR-532-3p (the passenger strand) are closely associated with poor prognosis of RCC patients . Ectopic expression of these miRNAs significantly attenuated the malignant phenotypes of RCC cells. A combination of genome-wide gene expression and in silico database analyses revealed AQP9 as a putative target oncogene regulated by miR-532-5p and miR-532-3p in RCC cells. High expression levels of AQP9 were significantly associated with poor prognosis of RCC patients, and aberrant AQP9 expression was detected in RCC clinical specimens. Knockdown of AQP9 inhibited the malignant phenotypes of RCC cells. Rescue assays of AQP9 overexpression showed that the miR-532/AQP9 axis was closely involved in RCC oncogenesis.

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、腎細胞癌における新規予後バイオマーカーや治療標的としての可能性を秘めており、本疾患の分子機構解明に有益な情報を提供できると考える。