The Ben May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
Nat Commun. 2013;4:1393. 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.
化疗耐药性经常导致肿瘤进展。然而，其潜在的分子机制尚不清楚。上皮-间充质转化已被证明与治疗耐药性相关，但功能联系和信号通路仍有待阐明。在这里，我们报告了 microRNA-30c，一种人类乳腺癌预后标志物，通过直接靶向肌动蛋白结合蛋白 twinfilin 1 发挥关键作用，促进上皮-间充质转化。白细胞介素-6 家族成员白细胞介素-11 被鉴定为 microRNA-30c 信号通路中 twinfilin 1 的二级靶点。microRNA-30c 在原发性乳腺癌中的表达与白细胞介素-11 的表达呈负相关，低水平的白细胞介素-11 与乳腺癌患者的无复发生存相关。我们的研究表明，microRNA-30c 在乳腺癌中受 GATA3 的转录调控。鉴定出一种新的 microRNA 介导的通路，可调节乳腺癌的化疗耐药性，将有助于开发新的治疗策略。
