Elucidation of molecular mechanism via NREF1 antisense RNA1 related to relapse of breast cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07580
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: National Cancer Center Japan
• Principal Investigator: Takeshita Fumitaka 国立研究開発法人国立がん研究センター, 研究所, 部門長 (40466199)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: long non-coding RNA

Outline of Final Research Achievements

NRF2F1-AS1, which was highly expressed in the primary tumor tissues of patients with breast cancer recurrence within 10 years after surgery, was suggested to be downregulated by estrogen and progesterone receptors. Breast cancer cells that overexpress NR2F1-AS1 showed slow cell proliferation both in culture conditions and when transplanted into nude mice. Additionally, these cells exhibited significantly increased expression levels of SOX2 and SOX9, which are known as cancer stem cell markers. These findings suggest that NR2F1-AS1 is involved in maintaining the dormancy of breast cancer cells, and regulating its expression is expected to contribute to the suppression of breast cancer recurrence.

Free Research Field

分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

乳がんの化学療法前のがん組織において、同定されている、再発や薬剤耐性に寄与する分子は少ない。さらに、がん細胞がストレスを受けた場合に変動する遺伝子数は、タンパク質にコードされる遺伝子よりも、lncRNAのほうが多いという報告があり、lncRNAの多くは核内でクロマチンの制御に関与してるが、がんの再発や抗がん剤耐性獲得に関与するlncRNAについての報告はまだ少ない。本研究で着目したNR2F1-AS1は、乳がんの休眠状態に関与するlncRNAと推測され、発現機序解明により、再発や抗がん剤耐性獲得に対する予防・治療への貢献が期待される。