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, Huiping Liu

Research output: Contribution to journalArticle

140 Scopus citations

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.

Original languageEnglish (US)
Article number1393
JournalNature communications
Volume4
DOIs
StatePublished - Oct 28 2013

    Fingerprint

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Bockhorn, J., Dalton, R., Nwachukwu, C., Huang, S., Prat, A., Yee, K., Chang, Y. F., Huo, D., Wen, Y., Swanson, K. E., Qiu, T., Lu, J., Young Park, S., Eileen Dolan, M., Perou, C. M., Olopade, O. I., Clarke, M. F., Greene, G. L., & Liu, H. (2013). MicroRNA-30c inhibits human breast tumour chemotherapy resistance by regulating TWF1 and IL-11. Nature communications, 4, [1393]. https://doi.org/10.1038/ncomms2393