Exploration and functional analysis of lncRNA associated with pituitary tumorigenesis

• Project/Area Number: 15K09432
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Kobe University
• Principal Investigator: Fukuoka Hidenori 神戸大学, 医学部附属病院, 助教 (80622068)
• Co-Investigator(Kenkyū-buntansha): 高橋 裕 神戸大学, 医学研究科, 准教授 (70301281)
• Co-Investigator(Renkei-kenkyūsha): YAMADA Shozo 虎の門病院, 間脳下垂体腫瘍外科 (80260131)
• Research Collaborator: YOSHIDA Kenichi
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: Cushing disease / long non-coding RNA / proliferation / invasiveness / ACTH / lncRNA / Cushing病 / 下垂体腺腫 / エピジェネティクス / 浸潤性 / miRNA / non-coding RNA / Lnc RNA / 内分泌腫瘍 / 細胞周期 / クッシング病 / 分子標的薬

Outline of Final Research Achievements

In this research, we explored long non-coding RNA (lncRNA)　which associated with proliferation and invasiveness in ACTH producing pituitary adenoma (ACTHoma). First, we divided specimens of ACTHoma from 7 patients according to Knosp grade; grade <2, and grade 2 and more, and compared their lncRNA expression levels using microarray analysis. Furthermore, we measured RNA levels of 30 ACTHoma specimens and compared with their clinical characterization. Then we found lncRNA CRNDE, which expressed 3.6 fold in tumors with grade 2 and more.
CRNDE expressed 3 fold in macroadenoma than in microadenoma, suggesting this lncRNA is associated with tumor proliferation in addition to invasiveness. CRNDE located in cytoplasm of ACTHoma, indicating the mechanism related to proliferation and invasiveness by CRNDE is mediated via microRNA or mRNA stability as an epigenetic regulation. Further molecular mechanism needs to be analyzed of CRNDE in ACTHoma as a potential therapeutic target.

Research Products

• [Journal Article] Multiple salivary cortisol measurements are a useful tool to optimize metyrapone treatment in patients with Cushing’s syndromes treatment; case presentations. (2018)
  • Author(s): Yoshida K, Fukuoka H, Odake Y, Nakajima S, Tachibana M, Ito J, Hosokawa Y, Yamada T, Miura H, Suematsu N, Matsumoto R, Bando H, Suda K, Nishizawa H, Iguchi G, Ogawa W, Takahashi Y
  • Journal Title: Front Endocrinol Volume: 8 Pages: 375-375
  • DOI: 10.3389/fendo.2017.00375
  • NAID: 120006382334
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cross-sectional prevalence of pancreatic cystic lesions in patients with acromegaly, a single-center experience (2017)
  • Author(s): Odake Yukiko、Fukuoka Hidenori、Yamamoto Masaaki、Arisaka Yoshifumi、Konishi Junya、Yoshida Kenichi、Matsumoto Ryusaku、Bando Hironori、Suda Kentaro、Nishizawa Hitoshi、Iguchi Genzo、Yamada Shozo、Ogawa Wataru、Takahashi Yutaka
  • Journal Title: Pituitary Volume: 20 Issue: 5 Pages: 509-514
  • DOI: 10.1007/s11102-017-0810-1
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] EGFR Induces E2F1-Mediated Corticotroph Tumorigenesis (2017)
  • Author(s): Takako Araki Xiaohai Liu Hiraku Kameda Yukiko Tone Hidenori Fukuoka Masahide Tone Shlomo Melmed
  • Journal Title: J. Endocr. Soc. Volume: 1 Issue: 2 Pages: 127-143
  • DOI: 10.1210/js.2016-1053
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] New potential targets for treatment of Cushing's disease: epithelial growth factor receptor and cyclin-dependent kinases. (2015)
  • Author(s): Hidenori Fukuoka
  • Journal Title: Pituitary Volume: 18(2) Issue: 2 Pages: 274-278
  • DOI: 10.1007/s11102-015-0637-6
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The prevalence and associated factors of colorectal neoplasms in acromegaly: a single center based study. (2015)
  • Author(s): Yamamoto M, Fukuoka H, Iguchi G, Matsumoto R, Takahashi M, Nishizawa H, Suda K, Bando H, Takahashi Y.
  • Journal Title: Pituitary Volume: 18 Issue: 3 Pages: 343-351
  • DOI: 10.1007/s11102-014-0580-y
  • Peer Reviewed / Open Access
• [Journal Article] Median-lower normal levels of serum thyroxine are associated with low triiodothyronine levels and body temperature in patients with central hypothyroidism. (2015)
  • Author(s): Hirata Y, Fukuoka H, Iguchi G, Iwahashi Y, Fujita Y, Hari Y, Iga M, Nakajima S, Nishimoto Y, Mukai M, Hirota Y, Sakaguchi K, Ogawa W, Takahashi Y.
  • Journal Title: Europian Journal of Endocrinology Volume: 173 Issue: 2 Pages: 247-256
  • DOI: 10.1530/eje-15-0130
  • Peer Reviewed / Open Access
• [Journal Article] A diagnostic pitfall in IgG4-related hypophysitis: infiltration of IgG4-positive cells in the pituitary of granulomatosis with polyangiitis. (2015)
  • Author(s): Bando H, Iguchi G, Fukuoka H, Taniguchi M, Kawano S, Saitoh M, Yoshida K, Matsumoto R, Suda K, Nishizawa H, Takahashi M, Morinobu A, Kohmura E, Ogawa W, Takahashi Y.
  • Journal Title: Pituitary Volume: 18 Issue: 5 Pages: 722-730
  • DOI: 10.1007/s11102-015-0650-9
  • Peer Reviewed / Open Access
• [Journal Article] The quality of life in acromegalic patients with biochemical remission by surgery alone is superior to that in those with pharmaceutical therapy without radiotherapy, using the newly developed Japanese version of the AcroQoL (2015)
  • Author(s): Yoshida K, Fukuoka H, Matsumoto R, Bando H, Suda K, Nishizawa H, Iguchi G, Ogawa W, Webb SM, Takahashi Y.
  • Journal Title: Pituitary Volume: 18 Issue: 6 Pages: 876-883
  • DOI: 10.1007/s11102-015-0665-2
  • Peer Reviewed / Open Access
• [Presentation] 下垂体腺腫発生に関わる分子学的異常の理解と診療への応用 (2018)
  • Author(s): 福岡秀規、吉田健一、小武由紀子、高橋裕
  • Organizer: 第27回間脳下垂体腫瘍学会
  • Invited
• [Presentation] ERBB4 in Cushing Pathogenesis (2017)
  • Author(s): Hidenori Fukuoka
  • Organizer: 15th International Pituitary Congress
  • Place of Presentation: Orlando
  • Year and Date: 2017-03-28
  • Int'l Joint Research / Invited
• [Presentation] Long noncoding RNA, CRNDEはACTH産生下垂体腺腫の増殖浸潤に関連する (2017)
  • Author(s): 吉田 健一、福岡 秀規、小武 由紀子、松本 隆作、坂東 弘教、隅田 健太郎、 西沢 衡、高橋 路子、井口 元三、山田 正三、小川 渉、高橋 裕
  • Organizer: 第27回間脳下垂体腫瘍学会
  • Place of Presentation: 東京
  • Year and Date: 2017-02-24
• [Presentation] 下垂体腺腫に対する分子標的薬の可能性 (2017)
  • Author(s): 福岡 秀規
  • Organizer: 第90回日本内分泌学会学術総会
  • Invited
• [Presentation] big ACTH分泌を認めたサブクリニカルクッシング病の一例 (2017)
  • Author(s): 小武由紀子、福岡秀規、高橋裕
  • Organizer: 第27回臨床内分泌代謝Update
• [Presentation] ERBB4 in Cushing's disease (2017)
  • Author(s): Hidenori Fukoka
  • Organizer: the 15th International Pituitary Congress
  • Int'l Joint Research / Invited
• [Presentation] Cushing病の腫瘍化メカニズムについて (2016)
  • Author(s): 福岡 秀規
  • Organizer: 第43回日本神経内分泌学会学術集会
  • Place of Presentation: 浜松
  • Year and Date: 2016-10-14
  • Invited
• [Presentation] ErbB signaling in the pathogenesis of corticotroph adenomas (2016)
  • Author(s): Hidenori Fukuoka
  • Organizer: International Symposium on Pituitary Gland and Related Systems2016
  • Place of Presentation: Hawaii
  • Year and Date: 2016-09-01
  • Int'l Joint Research / Invited
• [Presentation] ACTH産生下垂体腫瘍においてCyclin EはHOTAIRを負に制御する (2016)
  • Author(s): 吉田健一1)、福岡秀規2) 、小武由紀子1)、松本隆作1) 、坂東弘教1) 隅田健太郎1)、西澤衡2)、井口元三2)、小川渉1) 、高橋裕1)
  • Organizer: 第８９回日本内分泌学会学術総会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2016-04-21
• [Book] eLS (2017)
  • Author(s): Hidenori Fukuoka
  • Total Pages: 7
  • Publisher: John Wiley&Sons
• [Book] eLS, (2017)
  • Author(s): Hidenori Fukuoka
  • Publisher: John Wiley & Sons
• [Book] Endocrinologia Clinica - 6th Edition. (2016)
  • Author(s): Hidenori Fukuoka
  • Publisher: Saraiva
• [Book] クッシング症候群診療マニュアル (2015)
  • Author(s): 福岡 秀規
  • Total Pages: 3
  • Publisher: 診断と治療社