Investigation into the predictor of cetuximab effect based on microRNA in head and neck squamous cell carcinoma

• Project/Area Number: 26462596
• 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: Hanazawa Toyoyuki 千葉大学, 大学院医学研究院, 准教授 (90272327)
• Co-Investigator(Kenkyū-buntansha): 関 直彦 千葉大学, 大学院医学研究院, 准教授 (50345013)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 頭頸部扁平上皮癌 / マイクロRNA / セツキシマブ / 治療効果予測因子 / 上皮成長因子受容体 / 分子標的薬 / EGFR / 分子ネットワーク

Outline of Final Research Achievements

In this study, we newly constructed the RNA sequencing based miRNA expression signature by using clinical specimens. Based on the expression signature, we have identified several antitumor miRNAs and these miRNAs regulated oncogenic targets in head and neck squamous cell carcinoma (HNSCC) cells. miR-1 and miR-206 were significantly reduced HNSCC tissues and ectopic expression of these miRNAs inhibited HNSCC cancer cell aggressiveness. We found that two growth factor receptors, epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (c-MET), were directly regulated by both miR-1 and miR-206 in HNSCC cells. Moreover, several reports showed that EGFR inhibitors induced c-MET signal activation, suggesting a possible mechanism of acquired resistance to EGFR inhibitors. The identification of targets modulated by tumor-suppressive miR-1 and miR-206 may lead to a better understanding of molecular pathogenesis of HNSCC.

Research Products

• [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
• [Presentation] 頭頸部扁平上皮癌において癌抑制型miR-1/206はEGFRとc-METを制御する． (2016)
  • Author(s): 11.越塚 慶一, 花澤 豊行, 福本 一郎, 吉川 直子, 松下 良介, 俣木 浩子, 水野 圭子, 岡本 美孝, 関 直彦．
  • Organizer: 第75回日本癌学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-10-07