Functional analysis of oral cancer stem cell-related microRNAs and development of novel therapies

• Project/Area Number: 26861736
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Kumamoto University
• Principal Investigator: Yoshida Ryoji 熊本大学, 生命科学研究部, 講師 (10632458)
• Co-Investigator(Renkei-kenkyūsha): ITO Takaaki 熊本大学, 大学院生命科学研究部, 教授 (70168392) ; NAKAYAMA Hideki 熊本大学, 大学院生命科学研究部, 教授 (70381001)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 口腔癌 / マイクロRNA / 治療抵抗性 / 転移 / 口腔扁平上皮癌 / 浸潤 / インターロイキン6 / miRNA / 浸潤・転移

Outline of Final Research Achievements

The progression of treatment resistant cancer cells is a multistep and complicated process, frequently leading to a poor prognosis in cancer patients. Recently, growing evidence has indicated that deregulation of microRNAs (miRNAs) contributes to tumor progression in oral squamous cell carcinoma (OSCC),such as metastasis,chmoresistance and radioresistance. The purpose of this study was to investigate the functional significance of tumor-suppressive miRNA in cancer cells and to identify novel miRNA-mediated cancer pathways and responsible genes in treatment resistant OSCC, especially metastasis. In the present study, metastasis-related miRNA (tentative name; miR-X） has a tumor-suppressing role in metastasis in OSCC via regulating metastasis related molecules, suggesting miR-X as a potential new diagnostic and therapeutic target for the treatment of OSCC.

Research Products

• [Journal Article] The tumour stromal features are associated with resistance to 5-FU-based chemoradiotherapy and a poor prognosis in patients with oral squamous cell carcinoma. (2015)
  • Author(s): Matsuoka Y, Yoshida R, Nakayama H, Nagata M, Hirosue A, Tanaka T, Kawahara K, Nakagawa Y, Sakata J, Arita H, Hiraki A, Shinohara M.
  • Journal Title: APMIS Volume: 3 Issue: 3 Pages: 205-14
  • DOI: 10.1111/apm.12344
  • Peer Reviewed / Open Access
• [Journal Article] Osteopontin-integrin α(v)β(3) axis is crucial for 5-fluorouracil resistance in oral squamous cell carcinoma. (2015)
  • Author(s): Nakamura T, Shinriki S, Jono H, Ueda M, Nagata M, Guo J, Hayashi M, Yoshida R, Ota T, Ota K, Kawahara K, Nakagawa Y, Yamashita S, Nakayama H, Hiraki A, Shinohara M, Ando Y.
  • Journal Title: FEBS Lett Volume: 589 Issue: 2 Pages: 231-239
  • DOI: 10.1016/j.febslet.2014.12.004
  • Peer Reviewed / Open Access
• [Journal Article] Phase II clinical trial of multiple peptide vaccination for advanced head and neck cancer patients revealed induction of immune responses and improved OS (2015)
  • Author(s): Yoshitake, Y., Fukuma, D., Yuno, A., Hirayama, M., Nakayama, H., Tanaka. T., Nagata, M., Takamune, Y., Kawahara, K., Nakagawa, Y., Yoshida, R., Hirosue, A., Ogi, H., Hiraki, A. , Jono, H., Hamada, A., Yoshida, K., Nishimura, Y., Nakamura, Y., Shinohara, M.
  • Journal Title: Clinical Cancer Research Volume: 21 Issue: 2 Pages: 312-321
  • DOI: 10.1158/1078-0432.ccr-14-0202
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Notch1 controls cell invasion and metastasis in small cell lung carcinoma cell lines. (2014)
  • Author(s): Hassan Wael; Ryoji Yoshida; Shinji Kudoh; Kohki Hasegawa; Kanako Niimori-Kita; Takaaki Ito
  • Journal Title: Lung cancer Volume: 86(3) Issue: 3 Pages: 304-310
  • DOI: 10.1016/j.lungcan.2014.10.007
  • Peer Reviewed
• [Journal Article] Notch1 signaling controls cell proliferation, apoptosis and differentiation in lung carcinoma (2014)
  • Author(s): Hassan Wael; Ryoji Yoshida; Shinji Kudoh; Kohki Hasegawa; Kanako Niimori-Kita; Takaaki Ito
  • Journal Title: Lung Cancer Volume: 85(2) Issue: 2 Pages: 131-140
  • DOI: 10.1016/j.lungcan.2014.05.001
  • Peer Reviewed
• [Journal Article] Overexpression of nucleostemin contributes to an advanced malignant phenotype and a poor prognosis in oral squamous cell carcinoma. (2014)
  • Author(s): Yoshida R, Nakayama H, Nagata Y, Hirosue A, Tanaka T, Kawahara K, Nakagawa Y, Matsuoka Y, Sakata J, Akita H, Hiraki A, Shinohara M, and Ito T
  • Journal Title: Brit J Cancer Volume: 111 Issue: 12 Pages: 2308-2315
  • DOI: 10.1038/bjc.2014.539
  • Peer Reviewed / Open Access
• [Presentation] Investigation of the clinical significance of circulating miRNAs in oral squamous cell carcinoma (2015)
  • Author(s): Hikaru Nakashima, Ryoji Yoshida, Yuichiro Matsuoka, Masashi Nagata, Akiyuki Hirosue, Kenta Kawahara, Jyunki Sakata, Hidetaka Arita, Akimitsu Hiraki and Hideki Nakayama
  • Organizer: 第74会日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県、名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] IL-6 confers radioresistance via Nrf2 antioxidant pathway in oral squamous cell carcinoma cells (2015)
  • Author(s): Yuichiro Matsuoka, Ryoji Yoshida, Akiyuki Hirosue, Takuya Tanaka, Masashi Nagata, Kenta Kawahara, Hidetaka Arita, Junki Sakata, Hikaru Nakashima, Hidenao Ogi, Akimitsu Hiraki , Masanori Shinohara, Hideki Nakayama
  • Organizer: 第74会日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県、名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] 口腔扁平上皮癌細胞において腫瘍随伴マクロファージおよびIL-6は放射線耐性に寄与する (2015)
  • Author(s): 松岡 祐一郎、吉田 遼司、廣末 晃之、田中 拓也、永田 将士、川原 健太、有田 英生、坂田 純基、平木 昭光、篠原 正徳、中山 秀樹
  • Organizer: 第39回日本頭頸部癌学会・第4回アジア頭頸部癌学会
  • Place of Presentation: 神戸国際会議場（兵庫県、神戸市）
  • Year and Date: 2015-06-04
• [Presentation] 口腔扁平上皮癌患者におけるNeutrophil Lymphocyte Ratioの臨床的意義に関する検討 (2015)
  • Author(s): 中嶋 光、吉田 遼司、永田 将士、川原 健太、廣末 晃之、松岡 祐一郎、有田 英生、坂田 純基、平木 昭光、中山 秀樹
  • Organizer: 第69回日本口腔科学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府、大阪市）
  • Year and Date: 2015-05-13
• [Presentation] Prognostic impact of pretherapeutic laboratory values in oral squamous cell carcinoma. (2014)
  • Author(s): Hikaru Nakasima, Ryoji Yoshida, Yuichiro Matsuoka, Hideki Nakayama, Masashi Nagata, Akiyuki Hirosue, Kenta Kawahara, Yoshihiro Nakagawa, Hidetaka Arita, Jyunki Sakata, Akimitsu Hiraki, Masanori Shinohara
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 神奈川
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Radioresistance of metastatic tumor cells in oral squamous cell carcinoma. (2014)
  • Author(s): Yuichiro Matsuoka, Kenta Kawahara, Hideki Nakayama, Masashi Nagata, Ryoji Yoshida, Akiyuki Hirosue, Takuya Tanaka, Yoshihiro Nakagawa, Akimitsu Hiraki, and Masanori Shinohara
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 神奈川
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] The clinicopathological analysis of HMGA2 in oral suamous cell carcinoma. (2014)
  • Author(s): Junki Sakata, Akiyuki Hirosue, Ryoji Yoshida, Masafumi Nakamoto, Yuichirou Matsuoka, Arita Hideo, Kenta Kawahara, Yoshihiro Nakagawa, Masashi Nagata, Hideki Nakayama, Akimitsu Hiraki, Masanori Shinohara
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 神奈川
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] The clinical significance of FBXW7 in oral squamous cell carcinoma. (2014)
  • Author(s): Hidetaka Arita, Ryoji Yoshida, Yuichiro Matsuoka, Hideki Nakayama, Masashi Nagata, Akiyuki Hirosue, Kenta Kawahara, Yoshihiro Nakagawa, Jyunki Sakata, Akimitsu Hiraki, Masanori Shinohara
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 神奈川
  • Year and Date: 2014-09-24 – 2014-09-27