@article{f23fd494a35947b2a5fcd75840fb664b,
title = "MicroRNA-93 targets WASF3 and functions as a metastasis suppressor in breast cancer",
abstract = "Cancer cells with cancer stem cell (CSC) properties initiate both primary tumor formation and metastases at distant sites. Acquisition of CSC properties is highly associated with epigenetic alterations, including those mediated by microRNAs (miRNAs). We have previously established the breast cancer patient-derived tumor xenograft (PDX) mouse model in which CSC marker CD44+ cancer cells formed spontaneous microscopic metastases in the liver. In this PDX mouse, we found that the expression levels of 3 miRNAs (miR-25, miR-93, and miR-106b) in the miR-106b-25 cluster were much lower in the CD44+ human cancer cells metastasized to the liver than those at the primary site. Constitutive overexpression of miR-93 suppressed invasive ability and 3D-organoid formation capacity of breast cancer cells in vitro and significantly suppressed their metastatic ability to the liver in vivo. Wiskott-Aldrich syndrome protein family member 3 (WASF3), a regulator of both cytoskeleton remodeling and CSC properties, was identified as a functional target of miR-93: overexpression of miR-93 reduced the protein level of WASF3 in breast cancer cells and WASF3 rescued the miR-93-mediated suppression of breast cancer cell invasion. These findings suggest that miR-93 functions as a metastasis suppressor by suppressing both invasion ability and CSC properties in breast cancers.",
author = "Naoki Shibuya and Yoshihiro Kakeji and Yohei Shimono",
note = "Funding Information: We thank Drs. Miki Nishio, Jyunji Otani, Junko Mukohyama, Tomohiko Maehama and Tadaomi Takenawa (Kobe University, Japan), Taichi Isobe (Stanford University, USA), Masao Maeda and Takanori Hayashi (Fujita Health University, Japan), and Tatsunori Nishimura and Noriko Gotoh (Kanazawa University, Japan) for their superior support and discussions, Seishi Kono and Shintaro Takao (Kobe University) for collection of clinical specimens, and Hironobu Minami (Kobe University) for his superior mentorship. This work was supported by grants from the Japan Society for the Promotion of Science (JSPS KAKENHI) (15K14381, 18K07231, and Japan‐Belgium Research Cooperative Program to YS), the Princess Takamatsu Cancer Research Fund (to YS), the Fujita Health University (to YS), and the Cancer Research Institute of Kanazawa University (to YS). Funding Information: We thank Drs. Miki Nishio, Jyunji Otani, Junko Mukohyama, Tomohiko Maehama and Tadaomi Takenawa (Kobe University, Japan), Taichi Isobe (Stanford University, USA), Masao Maeda and Takanori Hayashi (Fujita Health University, Japan), and Tatsunori Nishimura and Noriko Gotoh (Kanazawa University, Japan) for their superior support and discussions, Seishi Kono and Shintaro Takao (Kobe University) for collection of clinical specimens, and Hironobu Minami (Kobe University) for his superior mentorship. This work was supported by grants from the Japan Society for the Promotion of Science (JSPS KAKENHI) (15K14381, 18K07231, and Japan-Belgium Research Cooperative Program to YS), the Princess Takamatsu Cancer Research Fund (to YS), the Fujita Health University (to YS), and the Cancer Research Institute of Kanazawa University (to YS). Publisher Copyright: {\textcopyright} 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.",
year = "2020",
month = jun,
day = "1",
doi = "10.1111/cas.14423",
language = "English",
volume = "111",
pages = "2093--2103",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Wiley-Blackwell",
number = "6",
}