miR-29-3p-familyの分子病態と制御 : 肝内胆管癌におけるITGA6とITGB1の関与

• 資料種別: 博士論文
• タイトル: miR-29-3p-familyの分子病態と制御 : 肝内胆管癌におけるITGA6とITGB1の関与
• 著者・編者: 保坂, 優斗
• 著者標目: 保坂, 優斗 ホザカ, ユウト
• 出版事項: MDPI
• 並列タイトル等: Molecular Pathogenesis and Regulation of the miR-29-3p-Family: Involvement of ITGA6 and ITGB1 in Intra-Hepatic Cholangiocarcinoma
• 授与機関名: 鹿児島大学
• 授与年月日: 2021-11-16
• 報告番号: 甲総研第623号
• 学位: 博士(医学); Doctor of Philosophy in Medical Science
• 本文の言語コード: eng
• 件名標目: intrahepatic cholangiocarcinoma; miR-29a-3p; miR-29b-3p; miR-29c-3p; tumor-suppressor; ITGA6; ITGB1; SP1
• 対象利用者: 一般
• 一般注記: 博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨; The aggressive nature of intrahepatic cholangiocarcinoma (ICC) renders it a particularly lethal solid tumor. Searching for therapeutic targets for ICC is an essential challenge in the development of an effective treatment strategy. Our previous studies showed that the miR-29-3p-family members (miR-29a-3p, miR-29b-3p and miR-29c-3p) are key tumor-suppressive microRNAs that control many oncogenic genes/pathways in several cancers. In this study, we searched for therapeutic targets for ICC using the miR-29-3p-family as a starting point. Our functional studies of cell proliferation, migration and invasion confirmed that the miR-29-3p-family act as tumor-suppressors in ICC cells. Moreover, in silico analysis revealed that “focal adhesion”, “ECM-receptor”, “endocytosis”, “PI3K-Akt signaling” and “Hippo signaling” were involved in oncogenic pathways in ICC cells. Our analysis focused on the genes for integrin-α6 (ITGA6) and integrin-β1 (ITGB1), which are involved in multiple pathways. Overexpression of ITGA6 and ITGB1 enhanced malignant transformation of ICC cells. Both ITGA6 and ITGB1 were directly regulated by the miR-29-3p-family in ICC cells. Interestingly, expression of ITGA6/ITGB1 was positively controlled by the transcription factor SP1, and SP1 was negatively controlled by the miR-29-3p-family. Downregulation of the miR-29-3p-family enhanced SP1-mediated ITGA6/ITGB1 expression in ICC cells. MicroRNA-based exploration is an attractive strategy for identifying therapeutic targets for ICC. Yuto Hozaka, Naohiko Seki, Takako Tanaka, Shunichi Asai, Shogo Moriya, Tetsuya Idichi, MasumiWada, Kiyonori Tanoue, Yota Kawasaki, Yuko Mataki, Hiroshi Kurahara, Takao Ohtsuka Molecular Pathogenesis and Regulation of the miR-29-3p-Family : Involvement of ITGA6 and ITGB1 in Intra-Hepatic Cholangiocarcinoma Cancers 2021, 13, 2804 https://doi.org/10.3390/cancers13112804
• 記録形式（IMT）: application/pdf
• オンライン閲覧公開範囲: インターネット公開
• 連携機関・データベース: 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
• 提供元機関・データベース: 鹿児島大学 : 鹿児島大学リポジトリ

目次

Result_Hozaka_Yuto_isk_623 other

Comments_Hozaka_Yuto_isk_623 other

Diss_保坂_優斗_ISK623_2021 fulltext

Abstract_保坂_優斗_4518810342_2021 abstract