Analysis of PRMT5 of epithelial-to-mesenchymal transition in oral cancer

• Project/Area Number: 19K10094
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57020:Oral pathobiological science-related
• Research Institution: Jichi Medical University
• Principal Investigator: Amano Yusuke 自治医科大学, 医学部, 学内准教授 (70571587)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: PRMT5 / 口腔癌 / 上皮間葉移行 / EMT

Outline of Research at the Start

本研究の目的は, 前研究課題の結果で示唆された口腔扁平上皮癌(OSCC)の浸潤先進部におけるPRMT5とEMTの関連を明らかにすることである. OSCCにおけるPRMT5 の機能解析は皆無である. 本研究課題を遂行することにより, PRMT5 のEMTを介したOSCCにおける進展過程が明らかに
なれば, OSCCの新たなepigenetic drug としての治療標的となり, 意義深いトランスレーショー
ナルリサーチとなり得る.

Outline of Final Research Achievements

We previously showed that the expression of PRMT5 was associated with EMT in
OSCC specimen. In the present study, I immunohistochemically examined examined associations between the expression of EMT markers and PRMT5 in surgically resected OSCC (n=118). In the YK-4C cases, showing spindle cell pattern, PRMT5 and PRMT1, another arginine methyltransferase, were highly expressed in the nuclei and cytoplasm of the cancer cells. Slug was expressed in the nuclei of the cancer cells. Statistical analyses showed that high expressions of PRMT1 and PRMT5 were significantly associated with high expression of slug. These findings raise the interesting possibility that PRMTs might be regulated in a coordinated manner in aggressive cancer cells that undergo EMT.

Academic Significance and Societal Importance of the Research Achievements

PRMT5の口腔癌EMT機構における役割において, Slugとの関連があることが明らかになった. また, 別のPRMTファミリーであるPRMT1も口腔癌EMT機構における役割を担っていることが明らかになった.

Research Products

• [Journal Article] ZEB1 expression is frequently detected in undifferentiated and de‐differentiated carcinomas, but is not specific among endometrial carcinomas (2022)
  • Author(s): Kihara Atsushi、Amano Yusuke、Fukushima Noriyoshi、Fujiwara Hiroyuki、Niki Toshiro
  • Journal Title: Histopathology Volume: 81 Issue: 1 Pages: 108-118
  • DOI: 10.1111/his.14671
  • Peer Reviewed
• [Journal Article] Infrequent loss of SMARCA4, SMARCA2, and SMARCB1 expression in uterine mesenchymal tumors. (2021)
  • Author(s): Kihara A, Amano Y, Matsubara D, Fukushima N, Fujiwara H, Niki T.
  • Journal Title: Hum Pathol. Volume: 116 Pages: 12-21
  • DOI: 10.1016/j.humpath.2021.07.001
  • Peer Reviewed
• [Journal Article] Solitary adrenal metastasis from salivary duct carcinoma of the parotid gland successfully treated by surgery (2021)
  • Author(s): Amano Yusuke、Tsuji Kentaro、Kihara Atshushi、Matsubara Daisuke、Fukushima Noriyoshi、Nishino Hiroshi、Niki Toshiro
  • Journal Title: Medicine Volume: 100 Issue: 2 Pages: e24011-e24011
  • DOI: 10.1097/md.0000000000024011
  • Peer Reviewed / Open Access
• [Journal Article] Expression and localisation of methylthioadenosine phosphorylase (MTAP) in oral squamous cell carcinoma and their significance in epithelial-to-mesenchy (2021)
  • Author(s): Yusuke Amano, Daisuke Matsubara, Atsushi Kihara, Hiroshi Nishino, Yoshiyuki Mori, Toshiro Niki
  • Journal Title: Pathology Volume: 54 Issue: 3 Pages: 294-301
  • DOI: 10.1016/j.pathol.2021.05.101
  • Peer Reviewed / Open Access
• [Journal Article] BRG1, INI1, and ARID1B Deficiency in Endometrial Carcinoma (2020)
  • Author(s): Kihara Atsushi、Amano Yusuke、Matsubara Daisuke、Fukushima Noriyoshi、Fujiwara Hiroyuki、Niki Toshiro
  • Journal Title: American Journal of Surgical Pathology Volume: 44 Issue: 12 Pages: 1712-1724
  • DOI: 10.1097/pas.0000000000001581
  • Peer Reviewed
• [Journal Article] Adenomyoepithelioma with a human epidermal growth factor receptor 2-fluorescence in situ hybridization-confirmed ductal carcinoma in situ component (2020)
  • Author(s): Amano Yusuke、Sakaguchi-Tamba Mio、Sasaki Yumiko、Oshiro Hisashi、Fukushima Noriyoshi、Fujita Takashi、Masuda Shinobu、Niki Toshiro
  • Journal Title: Medicine Volume: 99 Issue: 42 Pages: e22665-e22665
  • DOI: 10.1097/md.0000000000022665
  • Peer Reviewed / Open Access
• [Journal Article] Desmoplastic small round cell tumor showing solid proliferation with limited desmoplasia and confusing immunohistochemical findings: an autopsy report (2020)
  • Author(s): Kihara Atsushi、Takahashi Kazuya、Ishikawa Ayataka、Amano Yusuke、Matsubara Daisuke、Kanda Hiroaki、Sata Naohiro、Fukushima Noriyoshi、Niki Toshiro
  • Journal Title: Medical Molecular Morphology Volume: 1 Issue: 3 Pages: 1-6
  • DOI: 10.1007/s00795-019-00242-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Reciprocal expression of trefoil factor‐1 and thyroid transcription factor‐1 in lung adenocarcinomas (2020)
  • Author(s): Matsubara Daisuke、Yoshimoto Taichiro、Soda Manabu、Amano Yusuke、Kihara Atsushi、Funaki Toko、Ito Takeshi、Sakuma Yuji、Shibano Tomoki、Endo Shunsuke、Hagiwara Koichi、Ishikawa Shumpei、Fukayama Masashi、Murakami Yoshinori、Mano Hiroyuki、Niki Toshiro
  • Journal Title: Cancer Science Volume: 111 Issue: 6 Pages: 1-13
  • DOI: 10.1111/cas.14403
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Histological evidence for the cardiac safety of high-dose pegylated liposomal doxorubicin in a patient with HIV-associated Kaposi sarcoma: a case report and literature review. (2019)
  • Author(s): Ishihara A, Hatakeyama S, Suzuki J, Amano Y, Sasahara T, Toshima M, Morisawa Y.
  • Journal Title: BMC Infect Dis. Volume: 19(1) Issue: 1 Pages: 848-848
  • DOI: 10.1186/s12879-019-4500-7
  • Peer Reviewed / Open Access
• [Journal Article] Data on characteristics of reported cases of unilateral posterior reversible encephalopathy syndrome (PRES). (2019)
  • Author(s): Ozawa T, Tanaka R, Nagaoka R, Anan Y, Kim Y, Matsuzono K, Mashiko T, Koide R, Shimazaki H, Ohtani K, Amano Y, Kawai K, Fujimoto S.
  • Journal Title: Data Brief. Volume: 11;27 Pages: 104648-104648
  • DOI: 10.1016/j.dib.2019.104648
  • Peer Reviewed
• [Journal Article] Stromal p16 Expression Helps Distinguish Atypical Polypoid Adenomyoma From Myoinvasive Endometrioid Carcinoma of the Uterus (2019)
  • Author(s): Kihara Atsushi、Amano Yusuke、Yoshimoto Taichiro、Matsubara Daisuke、Fukushima Noriyoshi、Fujiwara Hiroyuki、Niki Toshiro
  • Journal Title: The American Journal of Surgical Pathology Volume: 43 Issue: 11 Pages: 1526-1535
  • DOI: 10.1097/pas.0000000000001320
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mucin 21 is a key molecule involved in the incohesive growth pattern in lung adenocarcinoma (2019)
  • Author(s): Yoshimoto Taichiro、Matsubara Daisuke、Soda Manabu、Ueno Toshihide、Amano Yusuke、Kihara Atsushi、Sakatani Takashi、Nakano Tomoyuki、Shibano Tomoki、Endo Shunsuke、Hagiwara Koichi、Fukayama Masashi、Denda‐Nagai Kaori、Irimura Tatsuro、Mano Hiroyuki、Niki Toshiro
  • Journal Title: Cancer Science Volume: 110 Issue: 9 Pages: 3006-3011
  • DOI: 10.1111/cas.14129
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A modified preauricular and transmandibular approach for surgical management of osteosarcoma of the mandibular condyle within the masticator space and infratemporal fossa: a case report. (2019)
  • Author(s): Noguchi T, Sugiura Y, Okada N, Tsuchiya Y, Hyasaka JI, Sasaguri KI, Sarukawa S, Fujita A, Amano Y, Mori Y.
  • Journal Title: J Med Case Rep. Volume: 13(1) Issue: 1 Pages: 58-58
  • DOI: 10.1186/s13256-019-1975-1
  • Peer Reviewed / Open Access
• [Journal Article] 総説 口腔領域の細胞診 (2019)
  • Author(s): 天野雄介, 鈴木智子, 大城久, 松原大祐, 福嶋敬宜, 森良之, 仁木利郎
  • Journal Title: 臨床検査栃木 Volume: Vol.14 No.2 Pages: 133-138
  • Peer Reviewed
• [Presentation] 口腔扁平上皮癌における腫瘍間質の組織学的評価 (2021)
  • Author(s): 天野雄介, 木原淳, 長谷川雅世, 三浦珠希, 松原大祐, 福嶋 敬宜, 仁木利郎
  • Organizer: 第110回日本病理学会総会
• [Presentation] The role of hippo pathway protein expression in oral squamous cell carcinoma (2021)
  • Author(s): 天野雄介, 松原大祐, 木原淳, 吉本多一郎, 仁木利郎
  • Organizer: 第80回日本癌学会学術総会
• [Presentation] The role of MTAP expression in oral cancer (2020)
  • Author(s): 天野雄介, 松原大祐, 木原淳, 仁木利郎
  • Organizer: 第109回日本病理学会総会
• [Presentation] 口腔扁平上皮癌における腫瘍間質の組織学的評価 (2020)
  • Author(s): 天野雄介, 木原淳, 松原大祐, 森良之, 西野宏, 仁木利郎
  • Organizer: 第44回頭頸部癌学会
• [Presentation] Expressions of YAP and phospho-YAP (S127) in oral cancer (2019)
  • Author(s): 天野雄介, 松原大祐, 木原淳, 吉本多一郎, 仁木利郎
  • Organizer: 第78回日本癌学会学術総会
• [Presentation] The role of YAP expression in oral cancer (2019)
  • Author(s): 天野雄介, 松原大祐, 木原淳, 吉本多一郎, 仁木利郎
  • Organizer: 第108回日本病理学会総会
• [Presentation] Atypical polypoid adenomyoma の間質成分の免疫組織化学的検討 (2019)
  • Author(s): 木原淳, 天野雄介, 吉本多一郎, 松原大祐, 福嶋敬宜, 仁木利郎
  • Organizer: 第108回日本病理学会総会
• [Presentation] 術前に膵液細胞診でセロトニン産生神経内分泌腫瘍と診断し得た1例 (2019)
  • Author(s): 池田恵理子，鈴木智子，中村香織，織田智博，二階堂貴章，郡 俊勝，柳田美樹，吉本多一郎， 天野雄介，福嶋敬宜
  • Organizer: 第60回日本臨床細胞学会総会
• [Presentation] 膵の EUS-FNA で経験した悪性リンパ腫 3 例の細胞像 (2019)
  • Author(s): 中村香織，天野雄介，織田智博，鈴木智子，栁田美樹，郡 俊勝，池田恵理子，大城 久， 仁木利郎，福嶋敬宜
  • Organizer: 第60回日本臨床細胞学会総会
• [Remarks] 自治医科大学病理学講座統合病理学部門
  • URL: http://www.jichi.ac.jp/pathol/