title: MicroRNA-30c inhibits human breast tumour chemotherapy resistance by regulating TWF1 and IL-11.
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.
authors: The Ben May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
authors: Jessica
authors: J
authors: Bockhorn
authors: Rachel
authors: R
authors: Dalton
authors: Chika
authors: C
authors: Nwachukwu
authors: Simo
authors: S
authors: Huang
authors: Aleix
authors: A
authors: Prat
authors: Kathy
authors: K
authors: Yee
authors: Ya-Fang
authors: YF
authors: Chang
authors: Dezheng
authors: D
authors: Huo
authors: Yujia
authors: Y
authors: Wen
authors: Kaitlin E
authors: KE
authors: Swanson
authors: Tyler
authors: T
authors: Qiu
authors: Jun
authors: J
authors: Lu
authors: Seo Young
authors: SY
authors: Park
authors: M Eileen
authors: ME
authors: Dolan
authors: Charles M
authors: CM
authors: Perou
authors: Olufunmilayo I
authors: OI
authors: Olopade
authors: Michael F
authors: MF
authors: Clarke
authors: Geoffrey L
authors: GL
authors: Greene
authors: Huiping
authors: H
authors: Liu
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D016000:Cluster Analysis; D003599:Cytoskeleton / Q000187:drug effects / Q000235:genetics; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D005260:Female; D050990:GATA3 Transcription Factor / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017370:Interleukin-11 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D013489:Suppression, Genetic / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C508611:IL11 protein, human; D017370:Interleukin-11; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D008840:Microfilament Proteins; C485188:TWF1 protein, human; D004317:Doxorubicin; D011505:Protein-Tyrosine Kinases