It appears you don't have support to open PDFs in this web browser. To view this file, Open with your PDF reader
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.
You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer
Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer
Details
1 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
2 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
3 Department of Pathology, Affiliated Drum Tower Hospital of Nanjing University, Medical School, Nanjing, China
4 Department of Biological Sciences & NIH-Sponsored Border Biomedical Research Center, The University of Texas at El Paso, El Paso, TX, United States of America
5 The Center for Molecular Carcinogenesis, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, United States of America
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; The Center for Molecular Carcinogenesis, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, United States of America