膵癌の分子病因 : 発癌性遺伝子に対するmiR-30c-5pとmiR-30c-2-3pの影響

• Material Type: 博士論文
• Title: 膵癌の分子病因 : 発癌性遺伝子に対するmiR-30c-5pとmiR-30c-2-3pの影響
• Author/Editor: 田中, 貴子
• Author Heading: 田中, 貴子 タナカ, タカコ
• Publication, Distribution, etc.: MDPI
• Alternative Title: Molecular pathogenesis of pancreatic ductal adenocarcinoma : impact of miR-30c-5p and miR-30c-2-3p regulation on oncogenic genes
• Degree grantor/type: 鹿児島大学
• Date Granted: 2021-03-17
• Dissertation Number: 甲総研第604号
• Degree Type: 博士(医学); Doctor of Philosophy in Medical Science
• Text Language Code: eng
• Subject Heading: pancreatic ductal adenocarcinoma; microRNA; tumor-suppressor; miR-30c-5p; miR-30c-2-3p; TOP2A
• Target Audience: 一般
• Note (General): 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; Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive types of cancer, and its prognosis is abysmal; only 25% of patients survive one year, and 5% live for five years. MicroRNA(miRNA) signature analysis ofPDACrevealed that both strands of pre-miR-30c (miR-30c-5p, guide strand; miR-30c-2-3p, passenger strand) were significantly downregulated, suggesting they function as tumor-suppressors in PDAC cells. Ectopic expression assays demonstrated that these miRNAs attenuated the aggressiveness of PDAC cells, e.g., cell proliferation, migration, and invasiveness. Through a combination of in silico analyses and gene expression data, we identified 216 genes as putative oncogenic targets of miR-30c-5p and miR-30c-2-3p regulation in PDAC cells. Among these, the expression of 18 genes significantly predicted the 5-year survival rates of PDAC patients (p < 0.01). Importantly, the expression levels of 10 genes (YWHAZ, F3, TMOD3, NFE2L3, ENDOD1, ITGA3, RRAS, PRSS23, TOP2A, and LRRFIP1) were found to be independent prognostic factors for patient survival (p < 0.01). We focused on TOP2A (DNA Topoisomerase II Alpha) and investigated its potential as a therapeutic target for PDAC. The overexpression of TOP2A and its transcriptional activators (SP1 and HMGB2) was detected in PDAC clinical specimens. Moreover, the knockdown of TOP2A enhanced the sensitivity of PDAC cells to anticancer drugs. Our analyses of the PDAC miRNA signature and tumor-suppressive miRNAs provide important insights into the molecular pathogenesis of PDAC. Takako Tanaka, Reona Okada, Yuto Hozaka, Masumi Wada, Shogo Moriya, Souichi Satake, Tetsuya Idichi, Hiroshi Kurahara, Takao Ohtsuka and Naohiko Seki Molecular Pathogenesis of Pancreatic Ductal Adenocarcinoma: Impact of miR-30c-5p and miR-30c-2-3p Regulation on Oncogenic Genes Cancers 2020, 12(10), 2731 https://doi.org/10.3390/cancers12102731
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• 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): 鹿児島大学 : 鹿児島大学リポジトリ

Table of Contents

Result_Tanaka_Takako_isk_604 other

Comments_Tanaka_Takako_isk_604 other

Diss_田中_貴子_ISK604_2020 fulltext

Abstract_田中_貴子_4518810226_2020 abstract