Development of novel therapeutic strategies in head and neck squamous cell carcinoma based on microRNA-mediated cancer pathways

• Project/Area Number: 15K10801
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Chiba University
• Principal Investigator: SEKI NAOHIKO 千葉大学, 大学院医学研究院, 准教授 (50345013)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: マイクロRNA / 頭頸部扁平上皮癌 / 癌抑制遺伝子 / インテグリン / 発現プロファイル / 機能性RNA / 癌抑制型マイクロRNA / 癌促進型マイクロRNA / 治療抵抗性 / EGFR / c-MET / MET / シグナル伝達 / 受容体

Outline of Final Research Achievements

In this study, we construct the microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC). Our signature revealed that a total of 160 miRNAs (44 upregulated and 116 downregulated) were aberrantly expressed in cancer tissues. Expression of miR-150-5p (guide strand miRNA) and miR-150-3p (passenger strand miRNA) were significantly silenced in cancer tissues. Ectopic expression of mature miRNAs, miR-150-5p and miR-150-3p inhibited cancer cell aggressiveness. We identified that integrin α3 (ITGA3) and integrin α6 (ITGA6) were coordinately regulated by these miRNAs in HNSCC cells.

Research Products

• [Journal Article] Passenger strand of miR-145-3p acts as a tumor-suppressor by targeting MYO1B in head and neck squamous cell carcinoma (2018)
  • Author(s): Yamada Y, Koshizuka K, Hanazawa T, Kikkawa N, Okato A, Idichi T, Arai T, Sugawara S, Katada K, Okamoto Y, Seki N.
  • Journal Title: International Journal of Oncology Volume: 52 Pages: 166-178
  • DOI: 10.3892/ijo.2017.4190
  • Peer Reviewed / Open Access
• [Journal Article] Deep sequencing-based microRNA expression signatures in head and neck squamous cell carcinoma: dual strands of pre-miR-150 as antitumor miRNAs. (2017)
  • Author(s): Koshizuka K, Hanazawa T, Fukumoto I, Kikkawa N, Okamoto Y, Seki N.
  • Journal Title: Oncotarget Volume: 印刷中 Issue: 18 Pages: 30288-30304
  • DOI: 10.18632/oncotarget.16327
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of ITGA3 by the anti-tumor miR-199 family inhibits cancer cell migration and invasion in head and neck cancer (2017)
  • Author(s): Koshizuka Keiichi、Hanazawa Toyoyuki、Kikkawa Naoko、Arai Takayuki、Okato Atsushi、Kurozumi Akira、Kato Mayuko、Katada Koji、Okamoto Yoshitaka、Seki Naohiko
  • Journal Title: Cancer Science Volume: 108 Issue: 8 Pages: 1681-1692
  • DOI: 10.1111/cas.13298
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of integrin &#x3B2;1-mediated oncogenic signalling by the antitumor <i>microRNA-29</i> family in head and neck squamous cell carcinoma (2017)
  • Author(s): Koshizuka Keiichi、Kikkawa Naoko、Hanazawa Toyoyuki、Yamada Yasutaka、Okato Atsushi、Arai Takayuki、Katada Koji、Okamoto Yoshitaka、Seki Naohiko
  • Journal Title: Oncotarget Volume: 9 Issue: 3 Pages: 3663-3676
  • DOI: 10.18632/oncotarget.23194
  • Peer Reviewed / Open Access
• [Journal Article] Dual-receptor (EGFR and c-MET) inhibition by tumor-suppressive miR-1 and miR-206 in head and neck squamous cell carcinoma. (2017)
  • Author(s): Koshizuka K, Hanazawa T, Fukumoto I, Kikkawa N, Matsushita R, Mataki H, Mizuno K, Okamoto Y, Seki N.
  • Journal Title: Journal of Human Genetics Volume: 62 Issue: 1 Pages: 113-121
  • DOI: 10.1038/jhg.2016.47
  • NAID: 40021036343
  • Peer Reviewed / Open Access
• [Journal Article] The tumor-suppressive microRNA-23b/27b cluster regulates the MET oncogene in oral squamous cell carcinoma. (2016)
  • Author(s): Fukumoto I, Koshizuka K, Hanazawa T, Kikkawa N, Matsushita R, Kurozumi A, Kato M, Okato A, Okamoto Y, Seki N.
  • Journal Title: Int J Oncol. Volume: 49（3） Issue: 3 Pages: 1119-29
  • DOI: 10.3892/ijo.2016.3602
  • Peer Reviewed / Open Access
• [Journal Article] Tumor-suppressive microRNAs (miR-26a/b, miR-29a/b/c and miR-218) concertedly suppressed metastasis-promoting LOXL2 in head and neck squamous cell carcinoma (2016)
  • Author(s): Ichiro Fukumoto, Naoko Kikkawa, Ryosuke Matsushita, Mayuko Kato, Akira Kurozumi, Rika Nishikawa, Yusuke Goto, Keiichi Koshizuka, Toyoyuki Hanazawa, Hideki Enokida, Masayuki Nakagawa, Yoshitaka Okamoto, Naohiko Seki
  • Journal Title: Journal of Human Genetics Volume: 61(2) Issue: 2 Pages: 109-118
  • DOI: 10.1038/jhg.2015.120
  • NAID: 40020742209
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] MicroRNA expression signature of oral squamous cell carcinoma: functional role of microRNA-26a/b in the modulation of novel cancer pathways. (2015)
  • Author(s): Fukumoto I, Hanazawa T, Kinoshita T, Kikkawa N, Koshizuka K, Goto Y, Nishikawa R, Chiyomaru T, Enokida H, Nakagawa M, Okamoto Y, Seki N.
  • Journal Title: Br J Cancer Volume: 112 Issue: 5 Pages: 891-900
  • DOI: 10.1038/bjc.2015.19
  • Peer Reviewed / Open Access
• [Remarks] 千葉大学大学院医学研究院 機能ゲノム学
  • URL: http://genomejet.jp/
• [Remarks] 千葉大学大学院医学研究院、機能ゲノム学
  • URL: http://genomejet.jp/