Molecular signature of head and neck squamous cell carcinoma after treatment failure based on functional RNA analysis

• Project/Area Number: 18K09338
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Chiba University
• Principal Investigator: SEKI NAOHIKO 千葉大学, 大学院医学研究院, 准教授 (50345013)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: マイクロRNA / 頭頸部扁平上皮癌 / miR-99a-5p / miR-99a-3p / マイクロRNA発現プロファイル / 癌抑制遺伝子 / 癌遺伝子 / miR-30e-5p / TCGA / 機能性RNA / 癌抑制型マイクロRNA / プロファイル / 治療抵抗性

Outline of Final Research Achievements

Based on our miRNA profile by RNA-sequencing in HNSCC, both strands of the miR-99a-duplex (miR-99a-5p: the guide strand, and miR-99a-3p: the passenger strand) are downregulated in cancer tissues. Ectopic expression assays showed that both miRNAs significantly inhibited cancer cell aggressiveness. Next, we screened miR-99a-3p regulated oncogenes involved in HNSCC pathogenesis. A total of 114 genes were identified as miR-99a-3p-regulated genes, and 10 genes (STAMBP, TIMP4, TMEM14C, CANX, SUV420H1, HSP90B1, PDIA3, MTHFD2, BCAT1, and SLC22A15) significantly predicted 5-year overall survival of the patients.

Academic Significance and Societal Importance of the Research Achievements

頭頸部扁平上皮癌は、全ての癌種において6番目に多い癌であり、毎年65万人が新たに診断され、40万人以上が本疾患により亡くなる。最初の診断時において、既に、遠隔転移を有する症例にしばしば遭遇する。進行癌患者に対する治療法は限定的であり、生命予後は極めて厳しい。頭頸部扁平上皮癌患者に対する新規診断法、新規治療法の開発は急務である。

Research Products

• [Journal Article] FAM64A: A Novel Oncogenic Target of Lung Adenocarcinoma Regulated by Both Strands of miR-99a (miR-99a-5p and miR-99a-3p) (2020)
  • Author(s): Mizuno Keiko、Tanigawa Kengo、Nohata Nijiro、Misono Shunsuke、Okada Reona、Asai Shunichi、Moriya Shogo、Suetsugu Takayuki、Inoue Hiromasa、Seki Naohiko
  • Journal Title: Cells Volume: 9 Issue: 9 Pages: 2083-2083
  • DOI: 10.3390/cells9092083
  • Peer Reviewed / Open Access
• [Journal Article] RNA sequencing-based microRNA expression signature in esophageal squamous cell carcinoma: oncogenic targets by antitumor miR-143-5p and miR-143-3p regulation (2020)
  • Author(s): Wada Masumi、Goto Yusuke、Tanaka Takako、Okada Reona、Moriya Shogo、Idichi Tetsuya、Noda Masahiro、Sasaki Ken、Kita Yoshiaki、Kurahara Hiroshi、Maemura Kosei、Natsugoe Shoji、Seki Naohiko
  • Journal Title: Journal of Human Genetics Volume: 65 Issue: 11 Pages: 1019-1034
  • DOI: 10.1038/s10038-020-0795-x
  • Peer Reviewed / Open Access
• [Journal Article] Replisome genes regulation by antitumor miR‐101‐5p in clear cell renal cell carcinoma (2020)
  • Author(s): Yamada Yasutaka、Nohata Nijiro、Uchida Akifumi、Kato Mayuko、Arai Takayuki、Moriya Shogo、Mizuno Keiko、Kojima Satoko、Yamazaki Kazuto、Naya Yukio、Ichikawa Tomohiko、Seki Naohiko
  • Journal Title: Cancer Science Volume: - Issue: 4 Pages: 1392-1406
  • DOI: 10.1111/cas.14327
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Regulation of Oncogenic Targets by the Tumor-Suppressive miR-139 Duplex (miR-139-5p and miR-139-3p) in Renal Cell Carcinoma (2020)
  • Author(s): Okada Reona、Goto Yusuke、Yamada Yasutaka、Kato Mayuko、Asai Shunichi、Moriya Shogo、Ichikawa Tomohiko、Seki Naohiko
  • Journal Title: Biomedicines Volume: 8 Issue: 12 Pages: 599-599
  • DOI: 10.3390/biomedicines8120599
  • Peer Reviewed / Open Access
• [Journal Article] Molecular Pathogenesis of Pancreatic Ductal Adenocarcinoma: Impact of miR-30c-5p and miR-30c-2-3p Regulation on Oncogenic Genes. (2020)
  • Author(s): Tanaka T, Okada R, Hozaka Y, Wada M, Moriya S, Satake S, Idichi T, Kurahara H, Ohtsuka T, Seki N.
  • Journal Title: Cancers Volume: 12 Issue: 10 Pages: 2731-2731
  • DOI: 10.3390/cancers12102731
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Regulation of Oncogenic Targets by miR-99a-3p (Passenger Strand of miR-99a-Duplex) in Head and Neck Squamous Cell Carcinoma (2019)
  • Author(s): Okada Reona、Koshizuka Keiichi、Yamada Yasutaka、Moriya Shogo、Kikkawa Naoko、Kinoshita Takashi、Hanazawa Toyoyuki、Seki Naohiko
  • Journal Title: Cells Volume: 8 Issue: 12 Pages: 1535-1535
  • DOI: 10.3390/cells8121535
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of KIF2A by Antitumor miR-451a Inhibits Cancer Cell Aggressiveness Features in Lung Squamous Cell Carcinoma (2019)
  • Author(s): Uchida Akifumi、Seki Naohiko、Mizuno Keiko、Yamada Yasutaka、Misono Shunsuke、Sanada Hiroki、Kikkawa Naoko、Kumamoto Tomohiro、Suetsugu Takayuki、Inoue Hiromasa
  • Journal Title: Cancers Volume: 11 Issue: 2 Pages: 258-258
  • DOI: 10.3390/cancers11020258
  • Peer Reviewed / Open Access
• [Journal Article] Molecular pathogenesis of esophageal squamous cell carcinoma: Identification of the antitumor effects of miR 145 3p on gene regulation. (2019)
  • Author(s): Shimonosono M, Idichi T, Seki N, Yamada Y, Arai T, Arigami T, Sasaki K, Omoto I, Uchikado Y, Kita Y, Kurahara H, Maemura K, Natsugoe S.
  • Journal Title: Int J Oncol. Volume: 54 Pages: 673-688
  • DOI: 10.3892/ijo.2018.4657
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Molecular Pathogenesis of Gene Regulation by the miR-150 Duplex: miR-150-3p Regulates TNS4 in Lung Adenocarcinoma (2019)
  • Author(s): Misono Shunsuke、Seki Naohiko、Mizuno Keiko、Yamada Yasutaka、Uchida Akifumi、Sanada Hiroki、Moriya Shogo、Kikkawa Naoko、Kumamoto Tomohiro、Suetsugu Takayuki、Inoue Hiromasa
  • Journal Title: Cancers Volume: 11 Issue: 5 Pages: 601-601
  • DOI: 10.3390/cancers11050601
  • Peer Reviewed / Open Access
• [Journal Article] Involvement of dual-strand of the miR-144 duplex and their targets in the pathogenesis of lung squamous cell carcinoma (2018)
  • Author(s): Uchida Akifumi、Seki Naohiko、Mizuno Keiko、Misono Shunsuke、Yamada Yasutaka、Kikkawa Naoko、Sanada Hiroki、Kumamoto Tomohiro、Suetsugu Takayuki、Inoue Hiromasa
  • Journal Title: Cancer Science Volume: 110 Issue: 1 Pages: 420-432
  • DOI: 10.1111/cas.13853
  • Peer Reviewed / Open Access
• [Journal Article] Downregulation of matrix metalloproteinase 14 by the antitumor miRNA, miR-150-5p, inhibits the aggressiveness of lung squamous cell carcinoma cells (2018)
  • Author(s): Suetsugu Takayuki、Koshizuka Keiichi、Seki Naohiko、Mizuno Keiko、Okato Atsushi、Arai Takayuki、Misono Shunsuke、Uchida Akifumi、Kumamoto Tomohiro、Inoue Hiromasa
  • Journal Title: International Journal of Oncology Volume: 52 Pages: 913-924
  • DOI: 10.3892/ijo.2017.4232
  • Peer Reviewed / Open Access
• [Journal Article] Passenger strand of miR-145-3p acts as a tumor-suppressor by targeting MYO1B in head and neck squamous cell carcinoma (2018)
  • Author(s): Yamada Y, Koshizuka K, Hanazawa T, Kikkawa N, Okato A, Idichi T, Arai T, Sugawara S, Katada K, Okamoto Y, Seki N.
  • Journal Title: International Journal of Oncology Volume: 52 Pages: 166-178
  • DOI: 10.3892/ijo.2017.4190
  • Peer Reviewed / Open Access
• [Journal Article] Antitumor miR-150-5p and miR-150-3p inhibit cancer cell aggressiveness by targeting SPOCK1 in head and neck squamous cell carcinoma. (2017)
  • Author(s): Koshizuka, K., T. Hanazawa, N. Kikkawa, K. Katada, A. Okato, T. Arai, T. Idichi, Y. Osako, Y. Okamoto and N. Seki
  • Journal Title: Auris Nasus Larynx Volume: - Issue: 4 Pages: 854-865
  • DOI: 10.1016/j.anl.2017.11.019
  • Peer Reviewed / Open Access