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

• Published in: Nature communications Vol. 4; no. 1; p. 1393
• Main Authors: Bockhorn, Jessica, Dalton, Rachel, Nwachukwu, Chika, Huang, Simo, Prat, Aleix, Yee, Kathy, Chang, Ya-Fang, Huo, Dezheng, Wen, Yujia, Swanson, Kaitlin E., Qiu, Tyler, Lu, Jun, Young Park, Seo, Eileen Dolan, M., Perou, Charles M., Olopade, Olufunmilayo I., Clarke, Michael F., Greene, Geoffrey L., Liu, Huiping
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2013; Nature Publishing Group
• Subjects: 631/337/384/331; 631/67/1059/2326; 631/80/84/2176; 692/699/67/1347; Animals; Biomarkers; Biomarkers, Tumor - metabolism; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer therapies; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - genetics; Chemotherapy; Cluster Analysis; Cytokines; Cytoskeleton - drug effects; Cytoskeleton - genetics; Doxorubicin - pharmacology; Doxorubicin - therapeutic use; Drug dosages; Drug resistance; Drug Resistance, Neoplasm - drug effects; Drug Resistance, Neoplasm - genetics; Epithelial-Mesenchymal Transition - drug effects; Epithelial-Mesenchymal Transition - genetics; Female; GATA3 Transcription Factor - metabolism; Gene Expression Profiling; Gene Expression Regulation, Neoplastic - drug effects; Humanities and Social Sciences; Humans; Interleukin-11 - genetics; Interleukin-11 - metabolism; Mice; Microfilament Proteins - genetics; Microfilament Proteins - metabolism; MicroRNAs; MicroRNAs - metabolism; multidisciplinary; Prognosis; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; Real-Time Polymerase Chain Reaction; Science; Science (multidisciplinary); Stem cells; Suppression, Genetic - drug effects; Tumors; Xenograft Model Antitumor Assays; United States > US; Illinois; Chicago Illinois
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms2393

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. The role of microRNAs in chemotherapy resistance remains to be elucidated. Bockhorn et al. report that microRNA-30c, a human breast tumour prognostic marker, has a key role by targeting the epithelial-to-mesenchymal transition promoter twinfilin 1 and downstream interleukin-11 expression.