Growth inhibition of head and neck squamous cell carcinoma cells by sgRNA based on TRUE gene silencing.

• Project/Area Number: 24592588
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Yokohama City University
• Principal Investigator: ORIDATE Nobuhiko 横浜市立大学, 医学(系)研究科(研究院), 教授 (90312355)
• Co-Investigator(Kenkyū-buntansha): NASHIMOTO Masayuki 新潟薬科大学, 応用生物科学部, 教授 (30228069) ; TAMURA Masato 北海道大学, 歯学研究科(研究院), 教授 (30236757)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 頭頸部癌 / TRUE gene silencing / 頭頸部癌治療 / small guide RNA / heptamer型 sgRNA / 低侵襲 / 化学療法併用放射線治療 / heptamer型sgRNA / TRUE gene silencing法 / RNA干渉 / cyclinD1 / 頭頸部癌細胞 / サイクリンＤ１ / 遺伝子発現抑制法 / tRNase ZL

Outline of Final Research Achievements

Head and neck squamous cell carcinoma (HNSCC) exhibits increased expression of cyclin D1. Previous studies have shown a correlation between poor prognosis of HNSCC and cyclin D1 overexpression. tRNase ZL-utilizing efficacious gene silencing (TRUE gene silencing) is one of the RNA-mediated gene expression control technologies that have therapeutic potential. This technology is based on a unique enzymatic property of mammalian tRNase ZL, which is that it can cleave any target RNA at any desired site by recognizing a pre-tRNA-like complex formed between the target RNA and an artificial small guide RNA (sgRNA). In this study, we designed several sgRNAs targeting human cyclin D1 mRNA to examine growth inhibition of HNSCC cells. Transfection of certain sgRNAs decreased levels of cyclin D1 mRNA and protein in HSC-2 and HSC-3 cells, and also inhibited their proliferation. The combination of these sgRNAs and cisplatin showed more than additive inhibition of cancer cell growth.

Research Products

• [Journal Article] Growth inhibition of head and neck squamous cell carcinoma cells by sgRNA targeting the cyclin D1 mRNA based on TRUE gene silencing. (2014)
  • Author(s): Iizuka S, Oridate N, Nashimoto M, Fukuda S, Tamura M.
  • Journal Title: PLoS One Volume: 9 Issue: 12 Pages: e114121-e114121
  • DOI: 10.1371/journal.pone.0114121
  • NAID: 120005540292
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Growth inhibition of head and neck squamous carcinoma cells by sgRNA targeting the cyclin D1 mRNA based on TRUE gene silencing. (2013)
  • Author(s): Satoshi Iizuka, Nobuhiko Oridate, Masayuki Nashimoto, Masato Tamura
  • Organizer: 第72回 日本癌学会
  • Place of Presentation: パシフィコ横浜（横浜市西区）
• [Presentation] Prognostic value of cyclin D1 expression in tumor-free surgical margins in head and neck squamous cell carcinomas. (2013)
  • Author(s): Nobuhiko Oridate, Tomohiro Sakashita, Goshi Nishimura, Masanori Komatsu, Masahiro Takahashi, Takahide Taguchi, Akihiro Homma, Satoshi Fukuda
  • Organizer: The 12th Taiwan-Japan Conference on Otolaryngology Head and Neck Surgery
  • Place of Presentation: Taipei, Taiwan
  • Invited