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

• 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
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: マイクロRNA / 薬剤耐性 / 口腔癌 / microRNA / miR-30a / 口腔扁平上皮癌細胞 / 5-FU耐性 / サイクリンE2

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] 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. (* Contributed equally)
  • Journal Title: J Oral Pathol Med. Volume: 43 Issue: 5 Pages: 350-6
  • DOI: 10.1111/jop.12140
  • Peer Reviewed / Open Access
• [Journal Article] 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. (* Contributed equally)
  • Journal Title: Int J Oncol. Volume: 44 Issue: 4 Pages: 1376-84
  • DOI: 10.3892/ijo.2014.2265
  • Peer Reviewed / Open Access
• [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
  • NAID: 10031144847
  • 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
  • NAID: 130001876862
  • 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
• [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 Pages: 455-63
  • Peer Reviewed
• [Journal Article] Histopathological changes in parotid and submandibular glands of patients treated (2012)
  • Author(s): Teshima K, Murakami R, Yoshida R, Nakayama H, Hiraki A, Hirai T, Nakaguchi Y,
  • Journal Title: J Radiat Res. Volume: 53 Pages: 492-6
  • 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 Int Volume: 9 Issue: 2 Pages: 33-37
  • DOI: 10.1016/s1348-8643(12)00008-0
  • NAID: 10031144847
  • Peer Reviewed
• [Journal Article] 九州沖縄地区医学部附属病院歯科口腔外科8施設における最近5年間の口腔顎顔面骨折の調査 (2012)
  • Author(s): 大谷泰志、福田浩子、高岡昌男、喜久田利弘、新垣敬一、砂川元、中山秀樹、篠原正徳、山下佳雄、後藤昌昭、神崎夕貴、河野憲司、秋森俊行、大矢亮一、楠川仁悟、吉岡泉、迫田隅男
  • Journal Title: 日本口腔顎顔面外傷学会誌 Volume: 11 Pages: 15-20
  • Peer Reviewed
• [Journal Article] 抜歯後に生じた下行性壊死性縦隔炎の1例 (2012)
  • Author(s): 髙宗康隆、平木昭光、赤崎幸太、吉武義泰、中山秀樹、篠原正徳
  • Journal Title: 日本口腔外科学会誌 Volume: 58 Pages: 332-6
  • NAID: 10031144901
  • Peer Reviewed
• [Journal Article] Overexpression of cIAP2 contributes to 5-FU resistance and a poor prognosis in oral squamous cell carcinoma. (2011)
  • Author(s): Nagata M, Nakayama H, Tanaka T, Yoshida R, Yoshitake Y, Fukuma D, Kawahara K, Nakagawa Y, Ota K, Hiraki A, Shinohara M.
  • Journal Title: Br J Cancer. Volume: 105 Issue: 9 Pages: 1322-30
  • DOI: 10.1038/bjc.2011.387
  • Peer Reviewed
• [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
• [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
• [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: パシフィコ横浜
• [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: パシフィコ横浜
• [Presentation] Preoperative Chemoradiotherapy with S-1 Followed by Surgery in Patient with Locally advanced Oral Squamous Cell Carcinoma: A Prospective Phase II Trial (2012)
  • Author(s): Nakayama H, Nagata M, Tanaka T, Kawahara K, Nakagawa Y, Yoshida R, Ota Y, Hirosue A, Ogi H, FukumaD, Nanba A, Yoshitake Y, Ota K, Hiraki A, and Shinohara M.
  • Organizer: 第51回大韓口腔顎顔面外科学会
  • Place of Presentation: 江原道竜平リゾートグリーンピアコンドミニアム、ヨンピョン（韓国）
• [Presentation] Upregulation of miR-30a contributes to 5-FU resistance in oral squamous cell carcinoma (2012)
  • Author(s): Kawahara K, Nakayama H, Nagata M, Yoshida R, Tanaka T, Nakagawa Y, Hirosue A, Ogi H, Fukuma D, Yoshitake Y, Ota K, Hiraki A, and Shinohara M.
  • Organizer: 第71回日本癌学会
  • Place of Presentation: ロイトン札幌・さっぽろ芸文館・札幌市教育文化会館、札幌市
• [Presentation] The antiapoptotic mechanism underlying drug resistance of oral squamous cell carcinoma (2012)
  • Author(s): Nakayama H, Nagata M, Kawahara K, Nakagawa Y, Yoshida R, Tanaka T, Hirosue A, Fukuma D, Ogi H, Yoshitake Y, Ota K, Hiraki A, and Shinohara M.
  • Organizer: 17th World Congress on Advances in Oncology and 15th International Symposium on Molecular Medicine
  • Place of Presentation: Creta Marisホテル、クレタ島（ギリシャ）
• [Presentation] 5-FU耐性口腔扁平上皮癌細胞におけるNF-kB活性化の意義 (2012)
  • Author(s): 川原健太、中山秀樹、永田将士、吉田遼司、田中拓也、中川純泰、廣末晃之、吉武義泰、太田和俊、平木昭光、篠原正徳
  • Organizer: 第36回日本頭頸部癌学会
  • Place of Presentation: 島根県民会館、松江市
• [Presentation] Immunohistochemical analysis of Dicer and Drosha in oral squamous cell carcinoma.
  • Author(s): Kenta Kawahara, Hideki Nakayama, Masashi Nagata, Takuya Tanaka, Yoshihiro Nakagawa, Ryoji Yoshida, Yoshihiro Yoshitake, Kazutoshi Ota, Akimitsu Hiraki, Masanori Shinohara
  • Organizer: 第70回日本癌学会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] 口腔扁平上皮癌におけるDrosha発現の免疫組織化学的検討
  • Author(s): 川原健太、中山秀樹、永田将士、吉田遼司、田中拓也、中川純泰、吉武義泰、太田和俊、平木昭光、牧正啓、篠原正徳
  • Organizer: 第35回日本頭頸部癌学会
  • Place of Presentation: ウインクあいち
• [Remarks]
  • URL: http://www2.kuh.kumamoto-u.ac.jp/oralsurgery/