Abstract

Dysregulation of miRNAs is important in breast cancer initiation and malignant progression. Recently we showed that miR-152 downregulation is associated with breast cancer development, yet the underlying mechanism of miR-152 remains to be well elucidated. In this study, we identified β-catenin as a new direct target of miR-152. MiR-152 inhibited cell proliferation by targeting and inhibiting both β-catenin and PKM2 expression. We found that miR-152 expression sensitized the breast cancer cells to paclitaxel treatment by inhibiting β-catenin and PKM2 expression. Intriguingly, IGF-1 induced β-catenin and PKM2 expression and enhanced β-catenin and PKM2 interaction. Subsequently, IGF-1-induced β-catenin and PKM2 complex translocated into the nucleus, which in turn activated expression of miR-152. These results suggested a regulatory circuit between miR-152, β-catenin and PKM2 in breast cancer. By using human clinical specimens, we also showed that miR-152 expression levels were negatively correlated with β-catenin and PKM2 levels in breast cancer tissues. Our findings provide new insights into a mechanism of miR-152 involved in β-catenin and PKM2 inhibition which would have clinical implication for the cancer development and new treatment option in the future.

Details

Title
IGF-1-mediated PKM2/β-catenin/miR-152 regulatory circuit in breast cancer
Author
Yi-Yang, Wen 1 ; Wei-Tao, Liu 1 ; Hao-Ran, Sun 1 ; Ge, Xin 1 ; Zhu-Mei, Shi 2 ; Wang, Min 1 ; Li, Wei 3 ; Jian-Ying, Zhang 4 ; Ling-Zhi, Liu 5 ; Bing-Hua, Jiang 6 

 State Key Laboratory of Reproductive Medicine, Key Laboratory of Human Functional Genomics of Jiangsu Province, Collaborative Innovation Center for Cancer Personalized Medicine, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention, and Treatment, Cancer Center, and Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu, China 
 State Key Laboratory of Reproductive Medicine, Key Laboratory of Human Functional Genomics of Jiangsu Province, Collaborative Innovation Center for Cancer Personalized Medicine, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention, and Treatment, Cancer Center, and Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu, China; Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China 
 Department of Pathology, Affiliated Drum Tower Hospital of Nanjing University, Medical School, Nanjing, China 
 Department of Biological Sciences & NIH-Sponsored Border Biomedical Research Center, The University of Texas at El Paso, El Paso, TX, United States of America 
 The Center for Molecular Carcinogenesis, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, United States of America 
 State Key Laboratory of Reproductive Medicine, Key Laboratory of Human Functional Genomics of Jiangsu Province, Collaborative Innovation Center for Cancer Personalized Medicine, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention, and Treatment, Cancer Center, and Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu, China; The Center for Molecular Carcinogenesis, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, United States of America 
Pages
1-10
Publication year
2017
Publication date
Nov 2017
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1967047519
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.