Identification of long non-coding RNAs potentially involved in oral squamous cell carcinoma

• Project/Area Number: 18K17174
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Sapporo Medical University
• Principal Investigator: nishiyama koyo 札幌医科大学, 医学部, 助教 (60749563)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 口腔がん / 口腔癌 / 長鎖非コードRNA / noncoding RNA

Outline of Final Research Achievements

In the present study, we identified lncRNAs functionally associated with OSCC. By analyzing RNA-seq datasets obtained from primary head and neck squamous cell carcinoma (HNSCC). Among those, we found that knocking down lncRNA (DLEU1)　strongly suppressed OSCC cell proliferation. DLEU1 knockdown also suppressed migration, invasion and xenograft formation by OSCC cells, which is suggestive of its oncogenic functionality. Microarray analysis revealed that DLEU1　knockdown significantly affects expression of a number of cancer-related genes in OSCC cells, including HAS3, CD44 and TP63, suggesting that DLEU1 regulates HA-CD44 signaling. Expression of DLEU1 was elevated in 71% of primary OSCC tissues, and high DLEU1 expression was associated with shorter overall survival of HNSCC patients. These data suggest that elevated DLEU1 expression contributes to OSCC development, and that DLEU1 may be a useful therapeutic target in OSCC.

Academic Significance and Societal Importance of the Research Achievements

今回、新規口腔がん関連lncRNAとしてDLEU1を同定した。DLEU1は口腔がん細胞において高頻度に発現上昇しており、そのノックダウンはin vitroでの増殖、遊走、浸潤、そしてin vivoでの腫瘍形成能を抑制したことから、有望な治療標的分子と考えた。DLEU1と相互作用する分子や、関与するシグナル経路など、詳細な分子機構にはいまだ不明な点が残されている。それらを解明するする事で、新規診断・治療法の開発につなげることができる可能性が示唆された。

Research Products

• [Journal Article] Screening for long noncoding RNAs associated with oral squamous cell carcinoma reveals the potentially oncogenic actions of DLEU1 (2018)
  • Author(s): Nishiyama K、Maruyama R、Niinuma T、Kai M、Kitajima H、Toyota M、Hatanaka Y、Igarashi T、Kobayashi J、Ogi K、Dehari H、Miyazaki A、Yorozu A、Yamamoto E、Idogawa M、Sasaki Y、Sugai T、Tokino Takashi、Hiratsuka H、Suzuki H
  • Journal Title: Cell Death & Disease Volume: 9 Issue: 8 Pages: 826-826
  • DOI: 10.1038/s41419-018-0893-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Screening for long noncoding RNAs associated with oral squamous cell carcinoma reveals the potentially oncogenic actions of DLEU1 (2018)
  • Author(s): Koyo Nishiyama, Reo Maruyama, Hiroshi Kitajima, Takeshi Niinuma, Kazuhiro Ogi, Hironari Dehari, Akihiro Miyazaki, Akira Yorozu, Eiichiro Yamamoto, Masahiro Kai, Takashi Tokino, Hiromu Suzuki
  • Organizer: 第77回日本癌学会学術総会