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

• DOI: 10.1038/ncomms2393
• Publication Date: 2013-01-22T09:27:20Z
• Authors: 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. O...; Michael F. Clarke; Geoffrey L. Greene; Huiping Liu
• Keywords: 0303 health sciences; Epithelial-Mesenchymal Transition; Cell Survival; Gene Expression Profiling; Microfilament Proteins; Breast Neoplasms; GATA3 Transcription Factor; Interleukin-11; Prognosis; 3. Good health; Gene Expression Regulation, Neoplastic; Mice; MicroRNAs; 03 medical and health sciences; Doxorubicin; Drug Resistance, Neoplasm; Cell Line, Tumor; Biomarkers, Tumor; Animals; Cluster Analysis; Humans; Female; Cytoskeleton

Chemotherapy resistance frequently drives tumour progression. However, the underlying molecular mechanisms are poorly characterized. Epithelial-to-mesenchymal transition (EMT) has been shown to correlate with therapy resistance, but the functional link and signalling pathways remain to be elucidated. We report here that miR-30c, a human breast tumour prognostic marker, plays a pivotal role in chemo-resistance by a direct targeting of TWF1, which encodes an actin-binding protein and promotes EMT. An IL-6 family member, IL-11 was identified as a secondary target of TWF1 in the miR-30c signalling pathway. Expression of miR-30c inversely correlated with TWF1 and IL-11 levels in primary breast tumours and low IL-11 correlated with relapse-free survival in breast cancer patients. Our study demonstrates that miR-30c is transcriptionally regulated by GATA3 in breast tumours. Identification of a novel miRNA-mediated pathway that regulates chemo-resistance in breast cancer will facilitate the development of novel therapeutic strategies.