Regulation of miRNAs located within the imprinted DLK1-DIO3 locus at 14q32 in pituitary adenomas

• Project/Area Number: 15K09435
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: The University of Tokushima
• Principal Investigator: YOSHIMOTO Katsuhiko 徳島大学, 大学院医歯薬学研究部(歯学系), 教授 (90201863)
• Co-Investigator(Kenkyū-buntansha): 岩田 武男 徳島大学, 大学院医歯薬学研究部(歯学系), 助教 (10350399) ; 水澤 典子 徳島大学, 大学院医歯薬学研究部(歯学系), 助教 (80254746)
• 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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 下垂体 / 腫瘍 / インプリンティング / DNAメチル化 / 下垂体腺腫 / microRNA / メチル化 / miRNA

Outline of Final Research Achievements

Among miRNAs up-regulated in GH-producing adenomas in miRNA microarray analysis, 14q32 miRNAs were included. In contrast, these miRNAs were down-regulated in FSH/LH- and ACTH-producing adenomas, and null-cell adenomas. The adenoma type-dependent expression pattern was confirmed with qRT-PCR analysis. Although DNA copy-number changes at the 14q32 locus were not detected in all adenomas examined, abnormal methylation of CpG sites in imprinted genes within the DLK1-DIO3 locus was observed in 2 GH-producing adenomas by methylation-specific MLPA. According to DNA methylation analysis by pyrosequencing and bisulfite sequencing, methylation levels were different at each individual CpG site in intergenic DMR and MEG3-DMR, which regulate maternal gene expression at the DLK1-DIO3 locus, in 2 GH-producing adenomas. In conclusion, 14q32 miRNAs were up-regulated in sporadic GH-producing adenomas and methylation abnormalities were observed in certain GH-producing adenomas.

Research Products

• [Journal Article] Growth hormone-producing pituitary adenomas in childhood and young adulthood: clinical features and outcomes. (2018)
  • Author(s): Nagata Y,Inoshita N,Fukuhara N,Yamaguchi-Okada M,Nishioka H,Iwata T,Yoshimoto K,Yamada S
  • Journal Title: Pituitary Volume: 21 Issue: 1 Pages: 1-9
  • DOI: 10.1007/s11102-017-0836-4
  • NAID: 120006503287
  • Peer Reviewed / Open Access
• [Presentation] 非機能性腺腫および ACTH 腺腫における 14q32 領域遺伝子の発現低下 (2017)
  • Author(s): 小野 信二、岩田武男、水澤典子、山田正三、吉本勝彦
  • Organizer: 第27回間脳下垂体腫瘍学会
  • Place of Presentation: 日経ホール＆カンファレンスルーム（東京都千代田区）
  • Year and Date: 2017-02-24
• [Presentation] 家族性下垂体腺腫の病因 (2016)
  • Author(s): 吉本勝彦
  • Organizer: 第89回日本内分泌学会学術総会
  • Place of Presentation: 国立京都国際会館 （京都府・京都市）
  • Year and Date: 2016-04-21
• [Presentation] 内分泌異常と線維性骨異形成症の合併から、McCune-Albright症候群と診断した一例 (2016)
  • Author(s): 加藤 朋子、波床朋信、村上隆亮、米光新、武呂誠司、藤澤一朗、岩田武男、吉本勝彦、井下 尚子、山田尚三、隠岐尚吾
  • Organizer: 第89回日本内分泌学会学術総会
  • Place of Presentation: 国立京都国際会館 （京都府・京都市）
  • Year and Date: 2016-04-21
• [Presentation] 下垂体腺腫の分子病理学 (2016)
  • Author(s): 吉本勝彦
  • Organizer: 第61回成長ホルモン研究会
  • Place of Presentation: ホテルキャッスルプラザ（愛知県名古屋市中村区）
  • Year and Date: 2016-02-27
  • Invited
• [Presentation] 下垂体腫瘍発生と原因遺伝子 (2015)
  • Author(s): 吉本勝彦
  • Organizer: 第25回 臨床内分泌代謝Update
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
  • Year and Date: 2015-11-27
• [Presentation] シンポジウム「MEN1の基礎と臨床」：腫瘍発生分子機構のoverview (2015)
  • Author(s): 吉本勝彦
  • Organizer: 第88回日本内分泌学会学術総会
  • Place of Presentation: ホテルニューオオタニ東京（東京都千代田区）
  • Year and Date: 2015-04-23
• [Presentation] シンポジウム「下垂体腺腫の診断と治療Update 2015」：下垂体腺腫の腫瘍化機構 (2015)
  • Author(s): 吉本勝彦
  • Organizer: 第88回日本内分泌学会学術総会
  • Place of Presentation: ホテルニューオオタニ東京（東京都千代田区）
  • Year and Date: 2015-04-23