Investigation of regulating system in histone mRNA and microRNA expression in upper digestive tract cancer

• Project/Area Number: 26461994
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Iwate Medical University
• Principal Investigator: Iwaya Takeshi 岩手医科大学, 医学部, 講師 (70405801)
• Co-Investigator(Kenkyū-buntansha): 若林 剛 岩手医科大学, 医学部, 教授 (50175064) ; 西塚 哲 岩手医科大学, 医学部, 教授 (50453311)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ヒストンmRNA / microRNA / 胃癌 / 食道癌 / microRNA 760 / 癌転移浸潤

Outline of Final Research Achievements

Upregulation of multiple histone mRNA and downregulation of several microRNA (miR-760, miR-1276, and miR-4766-5p) which were targeting 3' untranslated regions of histone mRNAs were observed in gastric adenocarcinoma and esophageal squamous cell carcinoma. However, overexpression of these microRNAs could not change the cellular function of histone mRNA expression in cancer cells. Therefore, another mechanism is thought to be involved in regulating histone mRNA and microRNAs except for direct binding od these RNAs. In this study, we proposed a new mechanism that circular RNA might act as microRNA sponges and downregulated histone mRNAs in gastric cancer cells.

Research Products

• [Journal Article] Downregulation of ST6GALNAC1 is associated with esophageal squamous cell carcinoma development. (2017)
  • Author(s): Iwaya T, Sawada G, Amano S, Kume K, Ito C, Endo F, Konosu M, Shioi Y, Akiyama Y, Takahara T, Otsuka K, Nitta H, Koeda K, Mizuno M, Nishizuka S, Sasaki A, Mimori K.
  • Journal Title: Int J Oncol. Volume: 50(2) Issue: 2 Pages: 441-447
  • DOI: 10.3892/ijo.2016.3817
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Integrated Multiregional Analysis Proposing a New Model of Colorectal Cancer Evolution. (2016)
  • Author(s): R. Uchi (他40名, 山本36番目)
  • Journal Title: PLoS Genetics Volume: 12 Issue: 2 Pages: 1-24
  • DOI: 10.1371/journal.pgen.1005778
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genomic Landscape of Esophageal Squamous Cell Carcinoma in a Japanese Population. (2016)
  • Author(s): G. Sawada (他43名, 山本21番目)
  • Journal Title: Gastroenterology Volume: 150 Issue: 5 Pages: 1171-1182
  • DOI: 10.1053/j.gastro.2016.01.035
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] α-Amanitin Restrains Cancer Relapse from Drug-Tolerant Cell Subpopulations via TAF15 (2016)
  • Author(s): Kume K, Ikeda M, Miura S, Ito K, Sato KA, Ohmori Y, Endo F, Katagiri H, Ishida K, Ito C, Iwaya T, Nishizuka SS
  • Journal Title: Sci Rep Volume: - Issue: 1 Pages: 25895-25895
  • DOI: 10.1038/srep25895
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Integrated Multiregional Analysis Proposing a New Model of Colorectal Cancer Evolution. (2016)
  • Author(s): Uchi R, Takahashi Y, Niida A, Shimamura T, Hirata H, Sugimachi K, Sawada G, Iwaya T, et al
  • Journal Title: PLoS Genet Volume: 18;12(2)
  • Peer Reviewed / Open Access
• [Journal Article] Individualized Mutation Detection in Circulating Tumor DNA for Monitoring Colorectal Tumor Burden Using a Cancer-Associated Gene Sequencing Panel. (2016)
  • Author(s): Sato KA, Hachiya T, Iwaya T, Kume K, Matsuo T, Kawasaki K, Abiko Y, Akasaka R, Matsumoto T, Otsuka K, Nishizuka SS
  • Journal Title: PLoS One Volume: 11 Issue: 1 Pages: e0146275-e0146275
  • DOI: 10.1371/journal.pone.0146275
  • Peer Reviewed / Open Access
• [Journal Article] Intestinal epithelial culture under an air-liquid interface: a tool for studying human and mouse esophagi. (2015)
  • Author(s): Yokobori T, Suzuki S, Miyazaki T, Sohda M, Sakai M, Tanaka N, Ozawa D, Hara K, Honjo H, Altan B, Fukuchi M, Ishii H, Iwatsuki M, Sugimachi K, Sudo T, Iwaya T, Nishida N, Mimori K, Kuwano H, Mori M.
  • Journal Title: Dis Esophagus. Volume: [Epub ahead of print] Issue: 7 Pages: 843-847
  • DOI: 10.1111/dote.12346
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Hyperglycemia 3 days after esophageal cancer surgery is associated with an increased risk of postoperative infection. (2014)
  • Author(s): Ito N, Iwaya T, Ikeda K, Kimura Y, Akiyama Y, Konosu M, Ishida K, Fujiwara H, Otsuka K, Nitta H, Kashiwaba M, Koeda K, Nishizuka S, Mizuno M, Sasaki A, Wakabayashi G.
  • Journal Title: J Gastrointest Surg Volume: 18 (9) Pages: 1547-56
  • Peer Reviewed / Open Access
• [Journal Article] .A compensatory role of NF-κB to p53 in response to 5-FU-based chemotherapy for gastric cancer cell lines. (2014)
  • Author(s): Endo F, Nishizuka SS, Kume K, Ishida K, Katagiri H, Ishida K, Sato K, Iwaya T, Koeda K, Wakabayashi G
  • Journal Title: Plos One Volume: 9 (2) Issue: 2 Pages: e90155-e90155
  • DOI: 10.1371/journal.pone.0090155
  • Peer Reviewed / Open Access
• [Presentation] Target sequenceによる食道癌変異遺伝子同定効率に関する検討 (2017)
  • Author(s): 岩谷 岳,遠藤 史隆, 西塚 哲, 秋山 有史, 塩井 義祐, 高原 武志, 大塚 幸喜, 新田 浩幸, 肥田 圭介, 水野 大, 佐々木 章
  • Organizer: 第117回日本外科学会
  • Place of Presentation: 横浜
  • Year and Date: 2017-04-27
• [Presentation] Mutation detection by target sequence analyses using tissue-specific panels in esophageal squamous cell carcinoma (2017)
  • Author(s): Takeshi Iwaya, Fumitaka Endo, Kohei Kume, Yasushi Sasaki, Takashi Tokino, Satoshi Nishizuka
  • Organizer: American Association for Cancer Research Annual Meeting 2017
  • Place of Presentation: Washington, D.C.
  • Year and Date: 2017-04-01
  • Int'l Joint Research
• [Presentation] Mutation detection by target sequence analyses using cancer-related gene p anel in esophageal squamous cell carcinoma (2016)
  • Author(s): Iwaya T, Fumitaka Endo, Kohei Kume, Yasushi Sasaki, Takashi Tokino, Genta Sawada, A tsushi Niida, Koshi Mimori, Satoshi Nishizuka
  • Organizer: 第75回日本癌学会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06
• [Presentation] Inhibition of phosphatidylinositol 3-kinase suppresses propagation of drug-tolerant cancer cell subpopulations enriched by 5-fluorouracil (2016)
  • Author(s): Satoshi S. Nishizuka1, Kaoru Ishida1, Yukimi Ohmori1, Kohei Kume1, Chie Ito1, Akari Konta1, Yuka Koizumi1, Mamoru Nukatsuka2, Takashi Kobunai2, Teiji Takechi2, Takeshi Iwaya1
  • Organizer: アメリカ癌学会
  • Place of Presentation: ニューオリンズ
  • Year and Date: 2016-04-20
  • Int'l Joint Research
• [Presentation] TAF15 as an important mediator of RNA polymerase II-dependent drug tolerance (2016)
  • Author(s): Kohei Kume, Kohei Ito, Takeshi Iwaya, Satoshi S. Nishizuka
  • Organizer: アメリカ癌学会
  • Place of Presentation: ニューオリンズ
  • Year and Date: 2016-04-19
  • Int'l Joint Research
• [Presentation] Multiple genes on chromosome 17q25 were involved in sporadic esophageal squamous cell carcinoma development (2016)
  • Author(s): Takeshi Iwaya1, Suburu Amano1, Fumitaka Endo1, Yuji Akiyama1, Yoshihiro Shioi1, Kohei Kume1, Satoshi Nishizuka1, Chie Ito1, Akira Sasaki1, Koshi Mimori2
  • Organizer: アメリカ癌学会
  • Place of Presentation: ニューオリンズ
  • Year and Date: 2016-04-18
  • Int'l Joint Research
• [Presentation] Downregulation of TMPRSS11B in squamous cell carcinoma (2016)
  • Author(s): Suburu Amano, Takeshi Iwaya, Satoshi Nishizuka, Kohei Kume, Chie Ito, Yuji Akiyama, Yoshihiro Shioi, Fumitaka Endo, Akira Sasaki
  • Organizer: アメリカ癌学会
  • Place of Presentation: ニューオリンズ
  • Year and Date: 2016-04-18
  • Int'l Joint Research
• [Presentation] Multiple genes on chromosome 17q25 were involved in sporadic esophageal sq uamous cell carcinoma development (2016)
  • Author(s): Takeshi Iwaya, Suburu Amano, Fumitaka Endo, Yuji Akiyama, Yoshihiro Shioi, Kohei Kume, Satotshi Nishizuka, Chie Ito, Akira Sasaki, Koshi Mimori
  • Organizer: American Association for Cancer Research Annual Meeting 2016
  • Place of Presentation: New Orleans, Louisiana
  • Year and Date: 2016-04-16
  • Int'l Joint Research
• [Presentation] 癌細胞・癌関連線維芽細胞におけるヒストンmRNA/microRNA 代謝経路を標的とした癌治療法開発に向けた基礎研究 (2015)
  • Author(s): 岩谷 岳
  • Organizer: 第17回外科分子細胞治療研究会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-04-16
• [Presentation] Overexpression of long noncoding RNA FTX was associated with colorectal ca ncer progression (2014)
  • Author(s): 岩谷 岳、高橋佑典, 澤田元太, 嶋村徹平, 佐藤慧, 伊藤千恵, 久米浩平, 西塚哲, 秋山有史 , 森正樹, 三森功士, 若林剛
  • Organizer: 第73回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Downregulation of ST6GALNAC1 on chromosome 17q25.1 was associated with esophageal squamous cell carcinoma development / Takeshi Iwaya (2014)
  • Author(s): Takeshi Iwaya, Yuji Akiyama, Masafumi Konosu, Yusuke Kimura, Fumitaka Endo, Keisuke Koeda, Akira Sasaki, Koshi mimori, Go Wakabayashi
  • Organizer: The International Society for Diseases of the Esophagus
  • Place of Presentation: バンクーバー
  • Year and Date: 2014-09-22 – 2014-09-24
• [Presentation] 胃癌進展を制御するmicroRNA 760に関する検討 (2014)
  • Author(s): 岩谷 岳、三森功士, 深川剛生, 秋山有史, 鴻巣正史, 肥田圭介, 西塚哲, 森正樹, 笹子三津 留, 若林剛
  • Organizer: 第69回日本消化器外科学会総会
  • Place of Presentation: 福島
  • Year and Date: 2014-07-16 – 2014-07-18
• [Presentation] MicroRNA 760 regulates gastric cancer progression by downregulation of his tone mRNA expression (2014)
  • Author(s): Takeshi Iwaya, Takeo Fukagawa, Yutaka Suzuki, Tomoya Sudo, Kaoru Ishida, Kohei Kume, Satoshi Nishizuka, Hisae Iinuma, Masaki Mori, Mitsuru Sasako, Go Wakabayashi, Koshi Mimori
  • Organizer: アメリカ癌学会
  • Place of Presentation: サンディエゴ
  • Year and Date: 2014-04-05 – 2014-04-09