Establishment of histopathological diagnosis based on expression mechanism of bladder carcinoma-specific molecules and microRNAs

• Project/Area Number: 18K07021
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Nara Medical University
• Principal Investigator: Fujii Tomomi 奈良県立医科大学, 医学部, 講師 (50623477)
• Co-Investigator(Kenkyū-buntansha): 大林 千穂 奈良県立医科大学, 医学部, 教授 (90223940) ; 島田 啓司 奈良県立医科大学, 医学部, 非常勤講師 (90336850)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 膀胱癌 / マイクロRNA / 分子マーカー / NACC1 / Urothelial carcinoma / microRNA / miRNA

Outline of Final Research Achievements

In the early stage of bladder carcinoma, there are few subjective symptoms, and by the time gross hematuria and dysuria appear, the cancer is often advanced. NACC1 is a target molecule of miR-331-3p, and miR-331-3p suppresses the expression of NACC1 and regulates the proliferation of bladder cancer cells.In this research project, we 1) clarified the function of NACC1 in bladder cancer at the molecular level regarding its role in cell proliferation, and 2) examined how the expression of NACC1 as a biomarker affects the morphological characteristics of bladder carcinoma using urothelial carcinoma tissues.

Academic Significance and Societal Importance of the Research Achievements

膀胱癌における分子診断や分子標的療法への応用としてmiRNAを含めた種々の分子が検討されてきているが、実用化されている分子は未だに存在していない。
また、膀胱癌では分子標的療法の開発が難しい理由として、癌細胞の分化や化性による細胞の変化が著しいことが挙げられる。そこで、膀胱癌細胞の分化に寄与するmiRNAを見出し、幹細胞マーカーの発現も含めて膀胱癌の性質について明らかにしつつあることは膀胱癌の新しい悪性度や予後予測判定に有効な分子マーカーとしての可能性を有していると考える。

Research Products

• [Journal Article] Molecular Analysis of Liquid-Based Cytological Specimen Using Virtually Positive Sputum with Adenocarcinoma Cells. (2020)
  • Author(s): Nishikawa T, Fujii T, Tatsumi S, Sugimoto A, Sekita-Hatakeyama Y, Shimada K, Yamazaki M, Hatakeyama K, Ohbayashi C.
  • Journal Title: Diagnostics (Basel) Volume: 10(2) Issue: 2 Pages: 84-84
  • DOI: 10.3390/diagnostics10020084
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Evaluation of DNA and RNA quality from archival formalin-fixed paraffin-embedded tissue for next-generation sequencing - Retrospective study in Japanese single institution. (2020)
  • Author(s): Fujii T, Uchiyama T, Matsuoka M, Myojin T, Sugimoto S, Nitta Y, Okabe F, Sugimoto A, Sekita-Hatakeyama Y, Morita K, Itami H, Hatakeyama K, Ohbayashi C.
  • Journal Title: Pathol Int. Volume: 70(9) Issue: 9 Pages: 602-611
  • DOI: 10.1111/pin.12969
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] HEG1-responsive microRNA-23b regulates cell proliferation in malignant mesothelioma cells (2020)
  • Author(s): Fujii Tomomi、Itami Hiroe、Uchiyama Tomoko、Morita Kohei、Nakai Tokiko、Hatakeyama Kinta、Sugimoto Aya、Shimada Keiji、Tsuji Shoutaro、Ohbayashi Chiho
  • Journal Title: Biochemical and Biophysical Research Communications Volume: － Issue: 4 Pages: 927-933
  • DOI: 10.1016/j.bbrc.2020.03.172
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Supplementary granulocyte macrophage colony-stimulating factor to chemotherapy and programmed death-ligand 1 blockade decreases local recurrence after surgery in bladder cancer. (2019)
  • Author(s): Miyake M, Hori S, Ohnishi S, Toritsuka M, Fujii T, Shimizu T, Owari T, Morizawa Y, Gotoh D, Itami Y, Nakai Y, Anai S, Torimoto K, Tanaka N, Fujimoto K.
  • Journal Title: Cancer Sci. Volume: 110(10) Issue: 10 Pages: 3315-3327
  • DOI: 10.1111/cas.14158
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] MicroRNAs in Smoking-Related Carcinogenesis: Biomarkers, Functions, and Therapy (2018)
  • Author(s): Tomomi Fujii, Keiji Shimada, Tokiko Nakai, Chiho Ohbayashi
  • Journal Title: J. Clin. Med. Volume: 7 Issue: 5 Pages: 98-98
  • DOI: 10.3390/jcm7050098
  • Peer Reviewed / Open Access
• [Journal Article] NACC1, as a Target of MicroRNA-331-3p, Regulates Cell Proliferation in Urothelial Carcinoma Cells (2018)
  • Author(s): Kohei Morita, Tomomi Fujii, , Hiroe Itami, Tomoko Uchiyama, Tokiko Nakai, Kinta Hatakeyama, Aya Sugimoto, Makito Miyake, Yasushi Nakai, Nobumichi Tanaka, Keiji Shimada, Masaharu Yamazaki, Kiyohide Fujimoto, Chiho Ohbayashi
  • Journal Title: cancers Volume: 10 Issue: 10 Pages: 347-347
  • DOI: 10.3390/cancers10100347
  • Peer Reviewed / Open Access
• [Presentation] 尿路上皮癌におけるNACC1,TP53, SOX9遺伝子変異解析 (2020)
  • Author(s): 藤井智美, 森田剛平, 伊丹弘恵, 内山智子, 島田啓司, 畠山金太, 三宅牧人, 藤本清秀, 大林千穂
  • Organizer: 第109回日本病理学会総会
• [Presentation] FFPE検体を用いたDNA、RNA抽出および核酸品質評価の検討 (2019)
  • Author(s): 藤井智美、内山智子、森田剛平、伊丹弘恵、中井登紀子、畠山金太、大林千穂
  • Organizer: 第108回日本病理学会総会
• [Presentation] ヒト尿路上皮癌に発現するNACC1は microRNA-331-3pの標的分子として細胞増殖を制御する (2018)
  • Author(s): 藤井智美、森田剛平、島田啓司、畠山金太、三宅牧人、藤本清秀、大林千穂
  • Organizer: 第77回日本癌学会学術総会