Analysis of androgen-regulated natural antisense RNA for the diagnosis and treatment of prostate cancer

• Project/Area Number: 25670678
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: The University of Tokyo
• Principal Investigator: TAKAYAMA Ken-ichi 東京大学, 医学部附属病院, 助教 (50508075)
• Co-Investigator(Kenkyū-buntansha): URANO Tomohiko 東京大学, 医学部附属病院, 講師 (20334386) ; INOUE Satoshi 東京大学, 医学部附属病院, 特任教授 (40251251)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 分子腫瘍学 / 内分泌学 / 病態医化学 / ゲノム医科学

Outline of Final Research Achievements

In this study, we investigated the role of antisense RNA, expressed in the antisense direction of protein coding gene, among long non-coding RNAs regulated by androgen receptor (AR) in prostate cancer. First, we identified a novel androgen-inducible non-coding RNA situated in the antisense region of CTBP1 gene, and then we named it as CTBP1-AS. We found the androgen-dependent accumulation of this antisense RNA in the nucleus of prostate cancer cells and the epigenetic mechanism for prostate cancer progression by CTBP1-AS. We also identified additional antisense RNAs regulated by androgen using directional RNA-seq analysis in prostate cancer cells.

Research Products

• [Journal Article] RUNX1, an androgen- and EZH2-regulated gene, has differential roles in AR-dependent and -independent prostate cancer (2015)
  • Author(s): Takayama K, Suzuki T, Tsutsumi S, Fujimura T, Urano T, Takahashi S, Homma Y, Aburatani H, Inoue S
  • Journal Title: Oncotarget Volume: 6 Pages: 2263-2276
  • Peer Reviewed
• [Journal Article] Systemic identification of estrogen-regulated genes in breast cancer cells through cap analysis of gene expression mapping (2014)
  • Author(s): Yamaga R, Ikeda K, Boele J, Horie-Inoue K, Takayama K, Urano T, Kaida K, Carninci P, Kawai J, Hayashizaki Y, Ouchi Y, de Hoon M, Inoue S
  • Journal Title: Biochem Biophys Res Commun Volume: 447 Issue: 3 Pages: 531-536
  • DOI: 10.1016/j.bbrc.2014.04.033
  • Peer Reviewed
• [Journal Article] CtBP2 modulates the androgen receptor to promote prostate cancer progression (2014)
  • Author(s): Takayama K, Suzuki T, Fujimura T, Urano T, Takahashi S, Homma Y, Inoue S
  • Journal Title: Cancer Res Volume: 74 Issue: 22 Pages: 6542-6553
  • DOI: 10.1158/0008-5472.can-14-1030
  • Peer Reviewed
• [Journal Article] Expression of androgen and estrogen signaling components and stem cell markers to predict cancer progression and cancer-specific survival in patients with metastatic prostate cancer (2014)
  • Author(s): Fujimura T, Takahashi S, Urano T, Takayama K, Sugihara T, Obinata D, Yamada Y, Kumagai J, Kume H, Ouchi Y, Inoue S, Homma Y
  • Journal Title: Clin Cancer Res Volume: 20 Issue: 17 Pages: 4625-4635
  • DOI: 10.1158/1078-0432.ccr-13-1105
  • Peer Reviewed
• [Journal Article] PAPD5-mediated 3' adenylation and subsequent degradation of oncomiR miR-21 is disrupted in proliferative disease (2014)
  • Author(s): Boele J, Persson H, Shin JW, Ishizu Y, Newie I, Søkilde R, Hawkins SM, Coarfa C, Ikeda K, Takayama K, Horie-Inoue K, Ando Y, Burroughs AM, Sasaki C, Suzuki C, Sakai M, Aoki S, Ogawa A, Hasegawa A, Lizio M, Kaida K, Teusink B, Carninci P, Suzuki H, Inoue S, Gunaratne P, Rovira C, Hayashizaki Y, de Hoon M
  • Journal Title: Proc Natl Acad Sci U S A Volume: 111 Issue: 31 Pages: 11467-11472
  • DOI: 10.1073/pnas.1317751111
  • Peer Reviewed
• [Journal Article] Pyrrole-imidazole polyamide targeted to break fusion sites in TMPRSS2 and ERG gene fusion represses prostate tumor growth (2014)
  • Author(s): Obinata D, Ito Akiko, Fujiwara K, Takayama K, Ashikari D, Murata Y, Yamaguchi K, Urano T, Fujimura T, Fukuda N, Soma M, Watanabe T, Nagase H, Inoue S, Takahashi S
  • Journal Title: Cancer Sci Volume: 105 Issue: 10 Pages: 1272-1278
  • DOI: 10.1111/cas.12493
  • Peer Reviewed / Open Access
• [Journal Article] Integrative analysis of FOXP1 function reveals a tumor suppressive effect in prostate cancer (2014)
  • Author(s): Takayama K, Suzuki T, Tsutsumi S, Fujimura T, Takahashi S, Homma Y, Urano T, Aburatani H, Inoue S
  • Journal Title: Mol Endocrinol Volume: 28 Issue: 12 Pages: 2012-2024
  • DOI: 10.1210/me.2014-1171
  • Peer Reviewed
• [Journal Article] Androgen-responsive long noncoding RNA CTBP1-AS promotes prostate cancer. (2013)
  • Author(s): Takayama K, Horie-Inoue K, Katayama S, Suzuki T, Tsutsumi S, Ikeda K, Urano T, Fujimura T, Takagi K, Takahashi S, Homma Y, Ouchi Y, Aburatani H, Hayashizaki Y, Inoue S
  • Journal Title: EMBO J Volume: 32 Issue: 12 Pages: 1665-1680
  • DOI: 10.1038/emboj.2013.99
  • Peer Reviewed
• [Journal Article] Transcriptional network of androgen receptor in prostate cancer progression (2013)
  • Author(s): Takayama K, Inoue S
  • Journal Title: Int J Urol Volume: 20 Issue: 8 Pages: 756-768
  • DOI: 10.1111/iju.12146
  • Peer Reviewed
• [Journal Article] Clinical significance of amyloid precursor protein in patients with testicular germ cell tumor. (2013)
  • Author(s): Yamada Y, Fujimura T, Takahashi S, Takayama K, Urano T, Murata T, Obinata D, Ouchi Y, Homma Y, Inoue S
  • Journal Title: Adv Urol Volume: 2013 Pages: 348438-348438
  • DOI: 10.1155/2013/348438
  • Peer Reviewed
• [Journal Article] MiR-424/503-mediated Rictor upregulation promotes tumor progression (2013)
  • Author(s): Oneyama C, Kito Y, Asai R, Ikeda J, Yoshida T, Okuzaki D, Kokuda R, Kakumoto K, Takayama K, Inoue S, Morii E, Okada M.
  • Journal Title: PLos ONE 2013 Volume: 8(11) Issue: 11 Pages: e80300-e80300
  • DOI: 10.1371/journal.pone.0080300
  • Peer Reviewed
• [Presentation] [研究奨励賞口演部門最優秀賞] 新規アンドロゲン応答遺伝子G3BP2によるドセタキセル抵抗性及び去勢抵抗性前立腺癌への進展メカニズムの解析 (2015)
  • Author(s): 芦苅大作、高山賢一、大日方大亮、浦野友彦、井上聡、高橋悟
  • Organizer: 第24回泌尿器科分子細胞研究会
  • Place of Presentation: JPタワー ホール＆カンファレンス（東京都・千代田区）
  • Year and Date: 2015-02-27 – 2015-02-28
• [Presentation] アンドロゲン受容体による転写プログラムの統合的解析により同定された新たなエピジェネティック制御機構 (2014)
  • Author(s): 高山賢一、井上聡
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] [第33回日本癌学会奨励賞（基礎）受賞講演] ゲノム医学アプローチによる前立腺癌におけるアンドロゲン受容体転写ネットワークの解明 (2014)
  • Author(s): Takayama K, Inoue S
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] [International Sessions] アンドロゲンにより制御される長鎖非コードRNAを介した前立腺癌における腫瘍増殖促進機構の解明 (2014)
  • Author(s): 高山賢一、井上聡
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] アンドロゲン応答性の脂質代謝酵素ACSL3 は去勢抵抗性前立腺がんの増殖に関与する (2014)
  • Author(s): 右田敏郎、高山賢一、大日方大亮、池田和貴、浦野友彦、高橋悟、曽我朋義、井上聡
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] ChIP-sequence法の活用による前立腺癌細胞における新たなアンドロゲン受容体シグナルの同定 (2014)
  • Author(s): 芦苅大作、高山賢一、浦野友彦、大日方大亮、井上聡、高橋悟
  • Organizer: 第102回日本泌尿器科学会総会
  • Place of Presentation: 神戸国際会議場（兵庫県・神戸市）
  • Year and Date: 2014-04-24 – 2014-04-27
• [Presentation] ピロール・イミダゾール・ポリアミド(PIP)を用いた前立腺癌関連融合遺伝子の発現抑制法の検討 (2014)
  • Author(s): 藤原恭子、大日方大亮、伊藤亜希子、高山賢一、浦野友彦、井上聡、相馬正義、高橋悟、永瀬浩喜、福田昇
  • Organizer: 第87回日本内分泌学会学術総会
  • Place of Presentation: 福岡国際会議場（福岡県・福岡市）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] [Best Poster賞受賞] Expression of androgen and estrogen signaling components and stem cell markers is highly predictive of cancer progression of metastatic prostate cancer (2014)
  • Author(s): Fujimura T, Takahashi S, Urano T, Kume H, Takayama K, Murata T, Yamada Y, Obinata D, Inoue S, Homma Y
  • Organizer: 29th Annual Congress of the European Association of Urology
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 2014-04-11 – 2014-04-15
• [Presentation] Polyamide targeting transcription of long chain acyl-CoA synthetase 3: A novel therapeutic approach for prostate cancer (2014)
  • Author(s): Obinata D, Takayama K, Fujiwara K, Fukuda N, Urano T, Ito A, Ashikari D, Murata T, Fujimura T, Ikeda K, Horie-Inoue K, Inoue S, Takahashi S
  • Organizer: 29th Annual Congress of the European Association of Urology
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 2014-04-11 – 2014-04-15
• [Presentation] 前立腺癌細胞におけるアンドロゲン応答性Non-coding RNAの同定ならびに機能解析 (2013)
  • Author(s): 高山賢一、堀江公仁子、池田和博、浦野友彦、大内尉義、井上聡
  • Organizer: 第86回日本内分泌学会学術総会
  • Place of Presentation: 仙台
• [Presentation] ホルモン療法体制前立腺がん細胞のエクソーム解析 (2013)
  • Author(s): 堀江公仁子、兒玉啓輔、高山賢一、池田和博、井上聡
  • Organizer: 第13回日本抗加齢医学会総会
  • Place of Presentation: 横浜
• [Presentation] Novel collaborating factors for androgen receptor form transcriptional networks and contribute to the progression of prostate cancer (2013)
  • Author(s): 高山賢一、浦野友彦、井上聡
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] [ワークショップ] アンドロゲン応答性長鎖非コードRNAを介するホルモン依存性腫瘍増殖機構の解明 (2013)
  • Author(s): 高山賢一、大内尉義、井上聡
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸