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• Project/Area Number: 19K08372
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Idogawa Masashi 札幌医科大学, 医学部, 准教授 (00404749)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 非コードRNA / 癌 / non-coding RNA / RNA-seq / ネットワーク解析 / lncRNA / p53

Outline of Research at the Start

公共データベースに登録されている消化器癌組織サンプルのRNA-seqのビッグデータを用いて，蛋白コード遺伝子およびlncRNAの発現を解析し，臨床属性との相関解析および発現ネットワーク解析により機能的に重要なハブlncRNA群を同定したい．次に，ハブlncRNA群について細胞株を用いてp53を始めとする癌関連転写因子と転写ネットワークに与える影響を解析することで，消化器癌病態における細胞生物学的機能について明らかにしたい．これによりlncRNAの寄与による未知の消化器癌病態を明らかにすることが可能となり，新規の消化器癌診断・治療法の開発につながる知見を得ることができる．

Outline of Final Research Achievements

Recently, many studies have revealed that long non-coding RNAs (lncRNAs) play important roles in cancers. To find lncRNAs contributing to colorectal cancers, we performed the screening of lncRNAs through the expression and survival analysis in TCGA dataset. The screening revealed that the expression of several lncRNAs is significantly increased in colorectal cancers compared with normal tissues and its high expression correlates with poor prognosis. The knockdown of these lncRNAs inhibited cell growth and promoted apoptosis in colorectal cancer cells. To confirm the effects of the most growth-suppressive lncRNA on gene expression, RNA-seq was performed. the lncRNA knockdown modified the expression of several p53-targeting apoptosis-related genes. These results suggest that the lncRNA contributes to colorectal cancer progression by promoting cell growth and inhibiting apoptosis via the expression change of p53-targeting genes.

Academic Significance and Societal Importance of the Research Achievements

癌の罹患数は年々増加の一途をたどっており，その診断治療法の開発が急務となっている．これまでゲノムDNAから転写されたメッセンジャーRNAから蛋白が作られることが知られていたが，近年，メッセンジャーRNAに似ているが蛋白が作られないRNAが多数存在し，それらが癌の進展に関わっていることが明らかとなった．本研究ではそのようなRNAに着目し，大腸癌における役割の一端を明らかにした．

Research Products

• [Journal Article] Predictive value of an exosomal microRNA-based signature for tumor immunity in cervical cancer patients treated with chemoradiotherapy. (2023)
  • Author(s): Someya M, Hasegawa T, Tsuchiya T, Kitagawa M, Fukushima Y, Gocho T, Mafune S, Ikeuchi Y, Kozuka Y, Idogawa M, Hirohashi Y, Torigoe T, Iwasaki M, Matsuura M, Saito T, Sakata KI.
  • Journal Title: Med Mol Morphol. Volume: 56(1) Issue: 1 Pages: 38-45
  • DOI: 10.1007/s00795-022-00338-5
  • Peer Reviewed
• [Journal Article] MYEOV overexpression induced by demethylation of its promoter contributes to pancreatic cancer progression via activation of the folate cycle/c-Myc/mTORC1 pathway (2023)
  • Author(s): Tange S, Hirano T, Idogawa M, Hirata E, Imoto I, Tokino T
  • Journal Title: BMC Cancer Volume: 23 Issue: 1 Pages: 85-85
  • DOI: 10.1186/s12885-022-10433-6
  • Peer Reviewed / Open Access
• [Journal Article] Anthrax toxin receptor 2 is a potential therapeutic target for non-small cell lung carcinoma with MET exon 14 skipping mutations (2022)
  • Author(s): Yamaguchi M, Hirai S, Idogawa M, Uchida H, Sakuma Y
  • Journal Title: Exp Cell Res Volume: 413 Issue: 2 Pages: 113078-113078
  • DOI: 10.1016/j.yexcr.2022.113078
  • Peer Reviewed / Open Access
• [Journal Article] Individualized circulating tumor <scp>DNA</scp> monitoring in head and neck squamous cell carcinoma (2022)
  • Author(s): Kogo Ryunosuke、Manako Tomomi、Iwaya Takeshi、Nishizuka Satoshi、Hiraki Hayato、Sasaki Yasushi、Idogawa Masashi、Tokino Takashi、Koide Ayaka、Komune Noritaka、Yasumatsu Ryuji、Nakagawa Takashi
  • Journal Title: Cancer Medicine Volume: - Issue: 21 Pages: 3960-3968
  • DOI: 10.1002/cam4.4726
  • Peer Reviewed / Open Access
• [Journal Article] Multiomics identifies the link between intratumor steatosis and the exhausted tumor immune microenvironment in hepatocellular carcinoma (2022)
  • Author(s): Murai Hiroki、Kodama Takahiro、Maesaka Kazuki、Tanaka Satoshi、Mita Eiji、Ohkawa Kazuyoshi、Hikita Hayato、Sakamori Ryotaro、Tatsumi Tomohide、Eguchi Hidetoshi、Morii Eiichi、Takehara Tetsuo
  • Journal Title: Hepatology Volume: 77 Issue: 1 Pages: 77-91
  • DOI: 10.1002/hep.32573
  • Peer Reviewed / Open Access
• [Journal Article] Dual inhibition of BCL2L1 and MCL1 is highly effective against RET fusion-positive or MET exon 14 skipping mutation-positive lung adenocarcinoma cells. (2022)
  • Author(s): Hirai S, Idogawa M, Sumi T, Yamaguchi M, Niki T, Sakuma Y.
  • Journal Title: Biochem Biophys Res Commun. Volume: 630 Pages: 24-29
  • DOI: 10.1016/j.bbrc.2022.09.039
  • Peer Reviewed
• [Journal Article] Downregulation of protein kinase C gamma reduces epithelial property and enhances malignant phenotypes in colorectal cancer cells (2022)
  • Author(s): Satow Reiko、Suzuki Yudai、Asada Shinobu、Ota Sae、Idogawa Masashi、Kubota Shiori、Ikeo Noi、Yoneda Atsuko、Fukami Kiyoko
  • Journal Title: iScience Volume: 25 Issue: 12 Pages: 105501-105501
  • DOI: 10.1016/j.isci.2022.105501
  • Peer Reviewed / Open Access
• [Journal Article] BHLHE41/DEC2 Expression Induces Autophagic Cell Death in Lung Cancer Cells and Is Associated with Favorable Prognosis for Patients with Lung Adenocarcinoma. (2021)
  • Author(s): Toshiyuki Nagata, Kentaro Minami, Masatatsu Yamamoto, Tsubasa Hiraki, Masashi Idogawa, Katsumi Fujimoto, Shun Kageyama, Kazuhiro Tabata, Kohichi Kawahara, Kazuhiro Ueda, Ryuji Ikeda, Yukio Kato, Masaaki Komatsu, Akihide Tanimoto, Tatsuhiko Furukawa, Masami Sato
  • Journal Title: International journal of molecular sciences Volume: 22 Issue: 21 Pages: 11509-11509
  • DOI: 10.3390/ijms222111509
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Functional Depletion of HSP72 by siRNA and Quercetin Enhances Vorinostat-Induced Apoptosis in an HSP72-Overexpressing Cutaneous T-Cell Lymphoma Cell Line, Hut78. (2021)
  • Author(s): Fujii K, Idogawa M, Suzuki N, Iwatsuki K, Kanekura T.
  • Journal Title: Int J Mol Sci. Volume: 22 Issue: 20 Pages: 11258-11258
  • DOI: 10.3390/ijms222011258
  • Peer Reviewed / Open Access
• [Journal Article] Early dynamics of circulating tumor DNA predict chemotherapy responses for patients with esophageal cancer (2021)
  • Author(s): Ryosuke Fujisawa , Takeshi Iwaya, Fumitaka Endo, Masashi Idogawa, Noriyuki Sasaki, Hayato Hiraki, Shoichiro Tange, Tomomi Hirano, Yuka Koizumi , Masakazu Abe, Tomoko Takahashi, Mizunori Yaegashi , Yuji Akiyama, Mari Masuda, Akira Sasaki, Fumiaki Takahashi, Yasushi Sasaki, Takashi Tokino, Satoshi S Nishizuka
  • Journal Title: Carcinogenesis Volume: 42(10) Issue: 10 Pages: 1239-1249
  • DOI: 10.1093/carcin/bgab088
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] ALK-positive atypical Spitz tumour with conspicuous rosette-like structures (2021)
  • Author(s): Minowa Tomoyuki、Hida Tokimasa、Horimoto Kohei、Kato Junji、Kamiya Takafumi、Sugita Shintaro、Idogawa Masashi、Saida Toshiaki、Hasegawa Tadashi、Tokino Takashi、Uhara Hisashi
  • Journal Title: European Journal of Dermatology Volume: 31 Issue: 2 Pages: 256-258
  • DOI: 10.1684/ejd.2021.3997
  • Peer Reviewed
• [Journal Article] DLEU1 promotes oral squamous cell carcinoma progression by activating interferon-stimulated genes (2021)
  • Author(s): Hatanaka Yui、Niinuma Takeshi、Kitajima Hiroshi、Nishiyama Koyo、Maruyama Reo、Ishiguro Kazuya、Toyota Mutsumi、Yamamoto Eiichiro、Kai Masahiro、Yorozu Akira、Sekiguchi Shohei、Ogi Kazuhiro、Dehari Hironari、Idogawa Masashi、Sasaki Yasushi、Tokino Takashi、Miyazaki Akihiro、Suzuki Hiromu
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 20438-20438
  • DOI: 10.1038/s41598-021-99736-5
  • Peer Reviewed / Open Access
• [Journal Article] Genetic analyses of a secondary poroma and trichoblastoma in a HRAS-mutated sebaceous nevus (2021)
  • Author(s): Minowa, Tomoyuki ; Kamiya, Takafumi ; Hida, Tokimasa ; Okura, Masae ; Kato, Junji ; Idogawa, Masashi ; Tange, Shoichiro ; Hirano, Tomomi ; Tokino, Takashi ; Uhara, Hisashi,
  • Journal Title: J Dermatol Volume: 48 Issue: 8 Pages: 1268-1272
  • DOI: 10.1111/1346-8138.15919
  • Peer Reviewed / Open Access
• [Journal Article] Genetic analyses of mosaic neurofibromatosis type 1 with giant caf?‐au‐lait macule, plexiform neurofibroma and multiple melanocytic nevi (2020)
  • Author(s): Hida Tokimasa、Idogawa Masashi、Okura Masae、Sugita Shintaro、Sugawara Taro、Sasaki Yasushi、Tokino Takashi、Yamashita Toshiharu、Uhara Hisashi
  • Journal Title: The Journal of Dermatology Volume: 47 Issue: 6 Pages: 658-662
  • DOI: 10.1111/1346-8138.15327
  • Peer Reviewed / Open Access
• [Journal Article] Renal angiomyolipoma (AML) harboring a missense mutation of TSC2 with copy-neutral loss of heterozygosity (CN-LOH) (2019)
  • Author(s): Idogawa Masashi、Hida Tokimasa、Tanaka Toshiaki、Ohira Noriaki、Tange Shoichiro、Sasaki Yasushi、Uhara Hisashi、Masumori Naoya、Tokino Takashi、Natori Hiroshi
  • Journal Title: Cancer Biology & Therapy Volume: 21 Issue: 4 Pages: 315-319
  • DOI: 10.1080/15384047.2019.1702406
  • Peer Reviewed
• [Journal Article] Prognostic Effect of Long Noncoding RNA NEAT1 Expression Depends on p53 Mutation Status in Cancer (2019)
  • Author(s): Idogawa, M. Nakase, H. Sasaki, Y. Tokino, T.
  • Journal Title: J Oncol Volume: 1 Pages: 4368068-4368068
  • DOI: 10.1155/2019/4368068
  • Peer Reviewed / Open Access
• [Journal Article] High filamin-C expression predicts enhanced invasiveness and poor outcome in glioblastoma multiforme (2019)
  • Author(s): Kamil M, Shinsato Y, Higa N, Hirano T, Idogawa M, Takajo T, Minami K, Shimokawa M, Yamamoto M, Kawahara K, Yonezawa H, Hirano H, Furukawa T, Yoshimoto K, Arita K.
  • Journal Title: Br J Cancer Volume: 120 Issue: 8 Pages: 819-826
  • DOI: 10.1038/s41416-019-0413-x
  • Peer Reviewed / Open Access
• [Presentation] p53標的遺伝子ARVCFはスプライシング変化によりp53の腫瘍抑制能を補助する (2020)
  • Author(s): 井戸川 雅史
  • Organizer: 第79回日本癌学会学術総会
• [Presentation] 新規p53標的遺伝子ARVCFはスプライシング変化を誘導し腫瘍抑制に寄与する (2019)
  • Author(s): 井戸川 雅史
  • Organizer: 第78回日本癌学会学術総会
• [Presentation] 新規p53標的遺伝子ARVCFはスプライシング変化を誘導し腫瘍抑制に寄与する (2019)
  • Author(s): 井戸川 雅史
  • Organizer: 第120回北海道癌談話会例会