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
学位博士(医学)
Doctor of Philosophy in Medical Science
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
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）