2021 Fiscal Year Final Research Report

Elucidation of therapeutic target molecular pathway by understanding tripli negative breast cancer and functional RNA integration

Research Project

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Project/Area Number	19K09049
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55010:General surgery and pediatric surgery-related
Research Institution	Fujita Health University (2020-2021) Kagoshima University (2019)
Principal Investigator	Toda Hiroko 藤田医科大学, 医学部, 助教 (90814301)
Co-Investigator(Kenkyū-buntansha)	新田吉陽鹿児島大学, 鹿児島大学病院, 医員 (20725733) 関直彦千葉大学, 大学院医学研究院, 准教授 (50345013) 喜島祐子藤田医科大学, 医学部, 教授 (60381175) 夏越祥次鹿児島大学, 医歯学域医学系, 教授 (70237577)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	乳癌 / トリプルネガティブ / マイクロRNA / miR-101-5p / GINS1
Outline of Final Research Achievements	To identify therapeutic targets for triple-negative breast cancer (TNBC), we created microRNA (miRNA) expression signature using RNA-sequencing technology. Analysis of the signature revealed that expression of miR-101-5p was significantly reduced in breast cancer (BrCa) tissues. The Cancer Genome Atlas (TCGA) database showed that low expression of miR-101-5p predicted poor prognosis in patients with BrCa (overall survival rate: p = 0.0316). Ectopic expression of miR-101-5p attenuated aggressive phenotypes, e.g. proliferation, migration, and invasion, in BrCa cells. We identified that GINS complex subunit 1 (GINS1) was directly regulated by miR-101-5p in BrCa cells. Knockdown assays showed that downregulation of GINS1 inhibited the malignant features of BrCa cells. Moreover, aberrant expression of GINS1 observed in BrCa clinical specimens, and high GINS1 expression significantly predicted poor prognosis in patients with BrCa (overall survival rate: P = 0.0126).
Free Research Field	乳腺外科
Academic Significance and Societal Importance of the Research Achievements	乳癌患者の約20％を占めるトリプルネガティブ乳癌（TNBC）は、明確な治療標的分子が見つかってない為、ホルモン療法や分子標的薬の治療効果が期待できない。その為、他のタイプの乳癌に比べ予後不良である。TNBC細胞の分子生物学的な特徴を明らかにし、治療法の開発に向けた基礎研究を行う事は社会的に重要である。