Exploration of the proliferation mechanism of prostate cancer via Super-Enhancer and its application to therapy

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18557
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Nagasawa Masayuki 滋賀医科大学, 医学部, 助教 (30750525)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 前立腺癌 / Super-Enhancer / MANCR / 上皮間葉転換

Outline of Final Research Achievements

We show that Super-Enhancer-associated genes specific for androgen receptor-negative CRPC PC3 cells include genes involved in migration and invasion, and that JQ1 impairs migration and invasion of PC3 cells. We identified a long non-coding RNA, MANCR, which was markedly down-regulated by JQ1, and found that BRD4 binds to the MANCR locus. MANCR knockdown led to a significant decrease in migration and invasion of PC3 cells. Furthermore, RNA sequencing analysis revealed that expression of the genes involved in migration and invasion was altered by MANCR knockdown. In summary, our data demonstrate that MANCR plays a critical role in migration and invasion of PC3 cells.

Free Research Field

泌尿器

Academic Significance and Societal Importance of the Research Achievements

前立腺癌は日本における男性の癌罹患率において第1位になっている。転移性前立腺癌は致死性になることもあり、特に去勢抵抗性前立腺癌においては予後が限られていることが分かっている。今回の研究から、去勢抵抗性前立腺癌における標的遺伝子となりえる遺伝子を同定した。今後、前立腺癌の予後予測因子や治療標的としての有用性を検討したい。