GHSR methylation‑dependent expression of a variant ligand and receptor of the ghrelin system induces thymoma tumorigenesis

• Material Type: 博士論文
• Title: GHSR methylation‑dependent expression of a variant ligand and receptor of the ghrelin system induces thymoma tumorigenesis
• Author/Editor: Tegshee, Bilguun; Kondo, Kazuya; Soejima, Shiho; Muguruma, Kyoka; Tsuboi, Mitsuhiro; Kajiura, Koichiro; Kawakami, Yukikiyo; Kawakita, Naoya; Toba, Hiroaki; Yoshida, Mitsuteru; Takizawa, Hiromitsu; Tangoku, Akira
• Author Heading: Tegshee, Bilguun; Kondo, Kazuya; Soejima, Shiho; Muguruma, Kyoka; Tsuboi, Mitsuhiro; Kajiura, Koichiro; Kawakami, Yukikiyo; Kawakita, Naoya; Toba, Hiroaki; Yoshida, Mitsuteru; Takizawa, Hiromitsu; Tangoku, Akira
• Publication, Distribution, etc.: Spandidos Publications
• Publication Date: 2021-09-17
• Publication Date (W3CDTF): 2021-09-17
• Alternative Title: GHSR遺伝子のメチル化に関連するグレリン系バリアントリガンドと受容体の発現は胸腺腫の腫瘍形成を誘導する; EXPRESSION OF GHRELIN SYSTEM CONSTITUENTS IN THYMIC EPITHELIAL TUMORS
• Periodical title: Oncology Letters
• No. or year of volume/issue: 22 5
• Volume: 22
• Issue: 5
• Pages: 793-
• ISSN (Periodical Title): ISSN : 1792-1074; ISSN : 1792-1082
• Degree grantor/type: 徳島大学
• Date Granted: 2022-03-23
• Dissertation Number: 甲第3608号
• Degree Type: 博士（保健学）
• Text Language Code: eng
• Subject Heading: ghrelin; GHSR; In‑1 ghrelin; thymoma; thymic carcinoma; thymic epithelial tumors
• Target Audience: 一般
• Note (General): Our previous study reported that the DNA methylation of growth hormone secretagogue receptor (GHSR) was significantly higher in thymoma or thymic carcinoma (TC) than in normal thymic tissue samples. Thymic epithelial tumors (TETs) with higher GHSR DNA methylation were associated with significantly worse prognosis than those with lower levels of DNA methylation. Diversified components of the ghrelin‑GHSR axis may exert opposing effects in cancer progression, depending on the cancer type in question. However, the precise function of the axis remains unclear. In the present study, the mRNA expression of five key components of the ghrelin system [native ligand ghrelin, variant ligand In‑1 ghrelin, native receptor GHSR1a, variant receptor GHSR1b and acylation enzyme ghrelin O‑acyltransferase (GOAT)] were examined in 58 TET samples by reverse transcription‑quantitative PCR, and protein expression of GHSR1a and GHSR1b was assessed in 20 TETs using immunohistochemistry. The results revealed that In‑1 ghrelin, GHSR1b (variant forms) and GOAT were more strongly expressed in thymoma compared with thymic‑adjacent tissue. By contrast, no significant differences were observed in the expression of ghrelin and GHSR1a (native forms) between thymoma and thymic tissue. The mRNA expression of In‑1 ghrelin and GHSR1b (variant forms) was positively associated with GHSR methylation in thymoma tissue samples. However, a relationship was not found between ghrelin, GHSR1a or GOAT expression (native forms) and GHSR methylation in thymoma. Immunohistochemical analysis revealed that mRNA expression of GHSR1a and GHSR1b generally correlated with expression of the corresponding protein, and that the expression of GHSR1b was increased in advanced‑stage TETs. These results indicate that the DNA methylation of GHSR is associated with a shift from native expression (ghrelin and GHSR1a) to variant expression (In‑1 ghrelin and GHSR1b), which induces the tumorigenesis of thymoma, but not TC.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): This work is licensed under a Creative Commons Attribution 4.0 International (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/)
• Related Material (DOI): 10.3892/ol.2021.13054
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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http://repo.lib.tokushima-u.ac.jp/files/public/11/116971/20220511150117401042/k3608_abstract.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/116971/20220511150117501369/k3608_review.pdf fulltext

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http://repo.lib.tokushima-u.ac.jp/files/public/11/116971/20220511150117743754/k3608_supple.pdf fulltext