Identification of tumor-suppressive microRNAs regulating metastatic pathways in HNSCC

• Project/Area Number: 24592590
• 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, 医学(系)研究科(研究院), 准教授 (50345013)
• Co-Investigator(Kenkyū-buntansha): HANAZAWA Toyoyuki 千葉大学, 大学院医学研究院, 准教授 (90272327)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: マイクロRNA / 下咽頭癌 / 癌抑制遺伝子 / 発現プロファイル / 頭頸部癌 / 分子ネットワーク / 転移 / 頭頸部扁平上皮癌 / ゲノム / 扁平上皮癌

Outline of Final Research Achievements

In this study, we have developed miRNA expression signatures of hypopharyngeal squamous cell carcinoma (HSCC) using clinical specimens. Using those data, we have investigated the specific roles of miRNAs in HSCC metastasis by examining the differentially expressed miRNAs. Our hypopharyngeal squamous cell carcinoma (HSCC) microRNA signature showed that miR-451a is significantly downregulated in cancer tissues, suggesting that miR-451a might act as a tumor suppressor.
Restoration of miR-451a in cancer cell lines revealed that this miRNA significantly inhibited cancer cell migration and invasion. Our data demonstrated that the gene coding for endothelial and smooth muscle cell-derived neuropilin-like molecule (ESDN/DCBLD2) was a direct target of miR-451a regulation.

Research Products

• [Journal Article] Downregulation of the microRNA-1/133a cluster enhances cancer cell migration and invasion in lung-squamous cell carcinoma via regulation of Coronin1C (2015)
  • Author(s): Mataki H, Enokida H, Chiyomaru T, Mizuno K, Matsushita R, Goto Y, Nishikawa R, Higashimoto I, Samukawa T, Nakagawa M, Inoue H, Seki N.
  • Journal Title: Journal of Human Genetics Volume: 60 Issue: 2 Pages: 53-61
  • DOI: 10.1038/jhg.2014.111
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Tumor-suppressive microRNA-206 as a dual inhibitor of MET and EGFR oncogenic signaling in lung squamous cell carcinoma (2015)
  • Author(s): Mataki H, Seki N, Chiyomaru T, Enokida H, Goto Y, Kumamoto T, Machida K, Mizuno K, Nakagawa M, Inoue H.
  • Journal Title: International Journal of Oncology Volume: 46 Issue: 3 Pages: 1039-1050
  • DOI: 10.3892/ijo.2014.2802
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of tumour suppressive microRNA-451a in hypopharyngeal squamous cell carcinoma based on microRNA expression signature (2014)
  • Author(s): Fukumoto I, Kinoshita T, Hanazawa T, Kikkawa N, Chiyomaru T, Enokida H, Yamamoto N, Goto Y, Nishikawa R, Nakagawa M, Okamoto Y, Seki N.
  • Journal Title: British Journal of Cancer Volume: 111 Issue: 2 Pages: 386-394
  • DOI: 10.1038/bjc.2014.293
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] microRNA-504 inhibits cancer cell proliferation via targeting CDK6 in hypopharyngeal squamous cell carcinoma. (2014)
  • Author(s): Kikkawa N, Kinoshita T, Nohata N, Hanazawa T, Yamamoto N, Fukumoto I, Chiyomaru T, Enokida H, Nakagawa M, Okamoto Y, Seki N.
  • Journal Title: Int J Oncol. Volume: 44(6) Issue: 6 Pages: 2085-92
  • DOI: 10.3892/ijo.2014.2349
  • Peer Reviewed / Open Access
• [Journal Article] Tumour-suppressive microRNA-29s inhibit cancer cell migration and invasion by targeting laminin-integrin signalling in head and neck squamous cell carcinoma. (2013)
  • Author(s): Kinoshita T, Nohata N, Hanazawa T, Kikkawa N, Yamamoto N, Yoshino H, Itesako T, Enokida H, Nakagawa M, Okamoto Y, Seki N.
  • Journal Title: Br J Cancer Volume: 109 Issue: 10 Pages: 2636-2645
  • DOI: 10.1038/bjc.2013.607
  • Peer Reviewed
• [Journal Article] Tumor suppressive microRNA-218 inhibits cancer cell migration and invasion through targeting laminin-332 in head and neck squamous cell carcinoma (2012)
  • Author(s): Kinoshita et al.
  • Journal Title: Oncotarget Volume: 3 Pages: 1386-1400
  • Peer Reviewed
• [Journal Article] The functional significance of microRNA-375 in human squamous cell carcinoma: aberrant expression and effects on cancer pathways. (2012)
  • Author(s): Kinoshita T, Hanazawa T, Nohata N, Okamoto Y, Seki N
  • Journal Title: J Hum Genet. Volume: 57 Issue: 9 Pages: 556-63
  • DOI: 10.1038/jhg.2012.75
  • NAID: 10031056783
  • Peer Reviewed
• [Journal Article] Tumour suppressors miR-1 and miR-133a target the oncogenic function of purine nucleoside phosphorylase (PNP) in prostate cancer (2012)
  • Author(s): Kojima S, Chiyomaru T, Kawakami K, Yoshino H, Enokida H, Nohata N, Fuse M, Ichikawa T, Naya Y, Nakagawa M, Seki N.
  • Journal Title: Br J Cancer Volume: 106(2) Issue: 2 Pages: 405-413
  • DOI: 10.1038/bjc.2011.462
  • Peer Reviewed
• [Remarks] 千葉大学大学院・医学研究院
  • 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