Preclinical study

Breast Cancer Research and Treatment

, Volume 137, Issue 2, pp 373-382

First online:

MicroRNA-30c targets cytoskeleton genes involved in breast cancer cell invasion

  • Jessica BockhornAffiliated withThe Ben May Department for Cancer Research, The University of ChicagoDepartment of Biochemistry and Molecular Biology, The University of Chicago
  • , Kathy YeeAffiliated withThe Ben May Department for Cancer Research, The University of Chicago
  • , Ya-Fang ChangAffiliated withThe Ben May Department for Cancer Research, The University of Chicago
  • , Aleix PratAffiliated withLineberger Comprehensive Cancer Center, The University of North Carolina at Chapel HillTranslational Genomics Group, Vall D′Hebron Institute of Oncology (VHIO)
  • , Dezheng HuoAffiliated withDepartment of Health Studies, The University of Chicago
  • , Chika NwachukwuAffiliated withCenter for Clinical Cancer Genetics, Department of Medicine, The University of Chicago
  • , Rachel DaltonAffiliated withThe Ben May Department for Cancer Research, The University of Chicago
  • , Simo HuangAffiliated withThe Ben May Department for Cancer Research, The University of Chicago
  • , Kaitlin E. SwansonAffiliated withThe Ben May Department for Cancer Research, The University of Chicago
    • , Charles M. PerouAffiliated withLineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill
    • , Olufunmilayo I. OlopadeAffiliated withCenter for Clinical Cancer Genetics, Department of Medicine, The University of Chicago
    • , Michael F. ClarkeAffiliated withThe Institute for Stem Cell Biology and Regenerative Medicine, Stanford University
    • , Geoffrey L. GreeneAffiliated withThe Ben May Department for Cancer Research, The University of Chicago Email author 
    • , Huiping LiuAffiliated withThe Ben May Department for Cancer Research, The University of ChicagoThe Institute for Stem Cell Biology and Regenerative Medicine, Stanford University Email author 

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Abstract

Metastasis remains a significant challenge in treating cancer. A better understanding of the molecular mechanisms underlying metastasis is needed to develop more effective treatments. Here, we show that human breast tumor biomarker miR-30c regulates invasion by targeting the cytoskeleton network genes encoding twinfilin 1 (TWF1) and vimentin (VIM). Both VIM and TWF1 have been shown to regulate epithelial-to-mesenchymal transition. Similar to TWF1, VIM also regulates F-actin formation, a key component of cellular transition to a more invasive mesenchymal phenotype. To further characterize the role of the TWF1 pathway in breast cancer, we found that IL-11 is an important target of TWF1 that regulates breast cancer cell invasion and STAT3 phosphorylation. The miR-30c-VIM/TWF1 signaling cascade is also associated with clinical outcome in breast cancer patients.

Keywords

miR-30c Breast tumor invasion TWF1 VIM IL-11