The Heterochronic microRNA let-7 Inhibits Cell Motility by Regulating the Genes in the Actin Cytoskeleton Pathway in Breast Cancer

Authors:
  • JGJinyi Guo
    Jinyi Guo
  • LZLan Zheng
    Lan Zheng
  • CLChunsheng Li
    Chunsheng Li
  • TZTim M. Zheng
    Tim M. Zheng
  • JTJanos L. Tanyi
    Janos L. Tanyi
  • SLShun Liang
    Shun Liang
  • MMMarco Mitidieri
    Marco Mitidieri
  • DKDionyssios Katsaros
    Dionyssios Katsaros
  • XZXia Zhao
    Xia Zhao
  • YZYoucheng Zhang
    Youcheng Zhang
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Abstract
The heterochronic gene let-7 serves as a tumor suppressor microRNA by targeting various oncogenic pathways in cancer cells. Considerable evidence indicates that reduced expression of let-7 might be associated with poor clinical outcome in patients with cancer. Here, we report that the expression levels of three let-7 family members, let-7a, let-7b, and let-7g, were significantly decreased in the patients with breast cancer with lymph node metastasis compared with those without lymph node metastasis. Enforced expression of let-7b significantly inhibits breast cancer cell motility and affects actin dynamics. Using bioinformatic and experimental approaches, four genes in the actin cytoskeleton pathway, including PAK1, DIAPH2, RDX, and ITGB8, were identified as let-7 direct targets. Blocking the expression of PAK1, DIAPH2, and RDX significantly inhibits breast cancer cell migration induced by let-7b repression. Our results indicate that reconstitution of let-7 expression in tumor cells could provide a novel therapeutic strategy for the treatment of metastatic disease. Mol Cancer Res; 11(3); 240–50. ©2013 AACR.

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