MicroRNA-30c inhibits human breast tumour chemotherapy resistance by regulating TWF1 and IL-11

Jessica Bockhorn, Rachel Dalton, Chika Nwachukwu, Simo Huang, Aleix Prat, Kathy Yee, Ya-Fang Chang, Dezheng Huo, Yujia Wen, Kaitlin E. Swanson, Tyler Qiu, Jun Lu, Seo Young Park, M. Eileen Dolan, Charles M. Perou, Olufunmilayo I. Olopade, Michael F. Clarke, Geoffrey L. Greene and Huiping Liu ()
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Jessica Bockhorn: The University of Chicago
Rachel Dalton: The University of Chicago
Chika Nwachukwu: Center for Clinical Cancer Genetics, The University of Chicago
Simo Huang: The University of Chicago
Aleix Prat: Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill
Kathy Yee: The University of Chicago
Ya-Fang Chang: The University of Chicago
Dezheng Huo: University of Chicago
Yujia Wen: The University of Chicago
Kaitlin E. Swanson: The University of Chicago
Tyler Qiu: The University of Chicago
Jun Lu: Yale Stem Cell Center and Yale Cancer Center, Yale University
Seo Young Park: University of Chicago
M. Eileen Dolan: The University of Chicago
Charles M. Perou: Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill
Olufunmilayo I. Olopade: Center for Clinical Cancer Genetics, The University of Chicago
Michael F. Clarke: The Institute for Stem Cell Biology and Regenerative Medicine, Stanford University
Geoffrey L. Greene: The University of Chicago
Huiping Liu: The University of Chicago

Nature Communications, 2013, vol. 4, issue 1, 1-14

Abstract: Abstract Chemotherapy resistance frequently drives tumour progression. However, the underlying molecular mechanisms are poorly characterized. Epithelial-to-mesenchymal transition has been shown to correlate with therapy resistance, but the functional link and signalling pathways remain to be elucidated. Here we report that microRNA-30c, a human breast tumour prognostic marker, has a pivotal role in chemoresistance by a direct targeting of the actin-binding protein twinfilin 1, which promotes epithelial-to-mesenchymal transition. An interleukin-6 family member, interleukin-11 is identified as a secondary target of twinfilin 1 in the microRNA-30c signalling pathway. Expression of microRNA-30c inversely correlates with interleukin-11 expression in primary breast tumours and low interleukin-11 correlates with relapse-free survival in breast cancer patients. Our study demonstrates that microRNA-30c is transcriptionally regulated by GATA3 in breast tumours. Identification of a novel microRNA-mediated pathway that regulates chemoresistance in breast cancer will facilitate the development of novel therapeutic strategies.

Date: 2013
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DOI: 10.1038/ncomms2393

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