MicroRNA-93 targets WASF3 and functions as a metastasis suppressor in breast cancer

Naoki Shibuya, Yoshihiro Kakeji, Yohei Shimono

研究成果: Article査読

11 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)2093-2103
ページ数11
ジャーナルCancer science
111
6
DOI
出版ステータスPublished - 01-06-2020

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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