MiRNA-21 induces epithelial to mesenchymal transition and gemcitabine resistance via the PTEN/AKT pathway in breast cancer
- 14 December 2015
- journal article
- Published by Springer Science and Business Media LLC in Tumor Biology
- Vol. 37 (6), 7245-7254
- https://doi.org/10.1007/s13277-015-4604-7
Abstract
Acquisition of gemcitabine resistance in breast cancer has not been fully clarified. Prior studies suggest that miRNAs are important to chemoresistance in solid tumors and we confirmed that miR-21 is involved in the development of gemcitabine resistance. Epithelial-to-mesenchymal transition (EMT) and AKT pathway activation were noted to be important to this resistance as well. PTEN, a direct target gene of miR-21, was significantly downregulated in gemcitabine-resistant breast cancer cells and restoration of PTEN expression blocked miR-21-induced EMT and gemcitabine resistance. Our data offer novel insight into gemcitabine resistance in breast cancer and suggest that miR-21 may be used to predict optimal breast cancer therapy and may be a potential therapeutic target for reversing gemcitabine resistance.Keywords
Funding Information
- National Natural Science Foundation of China (CN) (81372846)
- National Natural Science Foundation of China (CN) (81402188)
This publication has 40 references indexed in Scilit:
- Up-regulation of miR-21 Mediates Resistance to Trastuzumab Therapy for Breast CancerJournal of Biological Chemistry, 2011
- Activation of β-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like charactersBMC Cancer, 2011
- Targeting miRNAs involved in cancer stem cell and EMT regulation: An emerging concept in overcoming drug resistanceDrug Resistance Updates, 2010
- Epithelial to mesenchymal transition and breast cancerBreast Cancer Research, 2009
- Epithelial-Mesenchymal Transitions in Development and DiseaseCell, 2009
- Endogenous human microRNAs that suppress breast cancer metastasisNature, 2008
- Phosphorylation of β-Catenin by AKT Promotes β-Catenin Transcriptional ActivityPublished by Elsevier BV ,2007
- miR-21-mediated tumor growthOncogene, 2006
- Immunohistochemical and Genetic Evaluation of Deoxycytidine Kinase in Pancreatic Cancer: Relationship to Molecular Mechanisms of Gemcitabine Resistance and SurvivalClinical Cancer Research, 2006
- The functions of animal microRNAsNature, 2004