Elucidation of the mechanisms underlying drug resistance of oral cancer based on microRNA analysis and applications of the findings to novel diagnostic and therapeutic strategy

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592967
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Kumamoto University
• Principal Investigator: NAKAYAMA Hideki 熊本大学, 医学部附属病院, 講師 (70381001)
• Co-Investigator(Kenkyū-buntansha): SHINOHARA Masanori 熊本大学, 生命科学研究部, 教授 (90117127)
• Project Period (FY): 2011 – 2013
• Keywords: マイクロRNA / 薬剤耐性 / 口腔癌

Research Abstract

Five-FU-resistant oral squamous cell carcinoma cell lines expressed more miR-30a than the parent cells, thus resulting in increased G1-arrested cells. Luciferase assay revealed that miR-30a suppresses the translation of cyclin E2. MiR-30a targeting significantly increased the sensitivity to 5-FU of OSCC cells with upregulation of cyclin E2 and downregulation of G1-arrested cells. These results suggest that miR-30a could be a useful target for overcoming 5-FU resistance of OSCC.

Research Products

• [Journal Article] (* Contributed equally) A low Dicer expression is associated with resistance to 5-FU-based chemoradiotherapy and a shorter overall survival in patients with oral squamous cell carcinoma (2014)
  • Author(s): Kawahara K, Nakayama H, Nagata M, Yoshida R, Hirosue A, Tanaka T, Nakagawa Y, Matsuoka Y, Kojima T, Takamune Y, Yoshitake Y, Hiraki A, and Shinohara M
  • Journal Title: J Oral Pathol Med Volume: 43(5) Pages: 350-6
  • DOI: 10.1111/jop.12140
  • Peer Reviewed
• [Journal Article] (* Contributed equally) Overexpression of fibronectin confers cell adhesion‑mediated drug resistance (CAM-DR) against 5-FU in oral squamous cell carcinoma cells (2014)
  • Author(s): Nakagawa Y, Nakayama H, Nagata M, Yoshida R, Kawahara K, Hirosue A, Tanaka T, Yuno A, Matsuoka Y, Kojima T, Yoshitake Y, Hiraki A, and Shinohara M
  • Journal Title: Int J Oncol Volume: 44(4) Pages: 1376-84
  • DOI: 10.3892/ijo.2014.2265
  • Peer Reviewed
• [Journal Article] Stromal Expression of Neutrophil Gelatinase-Associated Lipocalin Correlates with Poor Differentiation and Adverse Prognosis in Oral Squamous Cell Carcinoma (2014)
  • Author(s): Shinriki S, Jono H, Ueda M, Obayashi K, Nakamura T, Ota K, Ota T, Sueyoshi T, Guo J, Hayashi M, Hiraki A, Nakayama H, Yamashita S, Shinohara M, Ando Y
  • Journal Title: Histopathology Volume: 64(3) Pages: 356-64
  • Peer Reviewed
• [Journal Article] The pathological significance of Notch1 in oral squamous cell carcinoma (2013)
  • Author(s): Yoshida R, Nagata M, Nakayama H, Niimori-Kita K, Hassan W, Tanaka T, Shinohara M, Ito T
  • Journal Title: Lab Invest Volume: 93(10) Pages: 1068-81
  • Peer Reviewed
• [Journal Article] Level of serum antibody against a periodontal pathogen is associated with atherosclerosis and hypertension (2013)
  • Author(s): Hanaoka Y, Soejima H, Yasuda O, Nakayama H, Nagata M, Matsuo K, Shinohara M, Izumi Y, Ogawa H
  • Journal Title: Hypertens Res Volume: 36(9) Pages: 829-33
  • Peer Reviewed
• [Journal Article] Reduced expression of nuclear factor kB in oral mucosa undergoing preoperative chemoradiotherapy (2012)
  • Author(s): Ikebe T, Yamasaki K, Takamune Y, Nakayama H, Shinohara M
  • Journal Title: Oral Science International Volume: 9(2) Pages: 33-7
  • Peer Reviewed
• [Journal Article] Histopathological changes in parotid and submandibular glands of patients treated with preoperative chemoradiation therapy for oral cancer (2012)
  • Author(s): Teshima K, Murakami R, Yoshida R, Nakayama H, Hiraki A, Hirai T, Nakaguchi Y, Tsujita N, Tomitaka E, Furusawa M, Yamashita Y, Shinohara M
  • Journal Title: J Radiat Res Volume: 53(3) Pages: 492-6
  • Peer Reviewed
• [Journal Article] Selective inhibition of nuclear factor-κB by nuclear factor-κB essential modulator-binding domain peptide suppresses the metastasis of highly metastatic oral squamous cell carcinoma (2012)
  • Author(s): Tanaka T, Nakayama H, Yoshitake Y, Irie A, Nagata M, Kawahara K, Takamune Y, Yoshida R, Nakagawa Y, Ogi H, Shinriki S, Ota K, Hiraki A, Ikebe T, Nishimura Y, Shinohara M
  • Journal Title: Cancer Sci Volume: 103(3) Pages: 455-63
  • Peer Reviewed
• [Presentation] The antiapoptotic mechanism underlying drug resistance of oral squamous cell carcinoma (2013)
  • Author(s): Nakayama H, Nagata M, Kawahara K, Nakagawa Y, and Shinohara M
  • Organizer: 21ST INTERNATIONAL CONFERENCE ON ORAL AND MAXILLOFACIAL SURGERY
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 20131021-24
• [Presentation] Overexpression of miR-30a confers 5-FU resistance by inhibiting cell proliferation via G1 phase arrest through targeting cyclin E2 in oral squamous cell carcinoma (2013)
  • Author(s): Kenta Kawahara, Hideki Nakayama, Masashi Nagata, Ryoji Yoshida, Takuya Tanaka, Yoshihiro Nakagawa, Akiyuki Hirosue, Yuichiro Matsuoka, Yoshihiro Yoshitake, Akimitsu Hiraki, and Masanori Shinohara
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2013-10-05
• [Presentation] Overexpressed fibronectin contributes to cell adhesion-mediated drug resistance in oral squamous cell carcinoma (2013)
  • Author(s): Yoshihiro Nakagawa, Hideki Nakayama, Ryoji Yoshida, Masashi Nagata, Kenta Kawahara, Takuya Tanaka, Akiyuki Hirosue, Yuichiro Matsuoka, Yasuo Takamune, Yoshihiro Yoshitake, Akimitsu Hiraki, and Masanori Shinohara
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2013-10-03
• [Remarks]
  • URL: http://www2.kuh.kumamoto-u.ac.jp/oralsurgery/