The PDGF-D/miR-106a/Twist1 pathway orchestrates epithelial-mesenchymal transition in gemcitabine resistance hepatoma cells
Metrics: PDF 2085 views | HTML 2248 views | ?
Rui Wang1, Yumei Li1, Yueyue Hou1, Qingling Yang2, Sulian Chen2, Xi Wang3, Zishu Wang1, Yan Yang1, Changjie Chen2, Zhiwei Wang4, Qiong Wu1
1Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China
2Department of Biochemistry and Molecular Biology, Bengbu Medical College, Anhui, China
3Department of Oncology, The 117th Hospital of PLA, Hangzhou, China
4The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University, Suzhou, China
Qiong Wu, e-mail: firstname.lastname@example.org
Zhiwei Wang, e-mail: email@example.com
Keywords: Hepatocellular carcinoma, EMT, PDGF-D, miR-106a, Twist
Received: December 16, 2014 Accepted: January 23, 2015 Published: February 11, 2015
Emerging evidence demonstrates that platelet-derived growth factor-D (PDGF-D) plays a critical role in epithelial-mesenchymal transition (EMT) and drug resistance in hepatocellular carcinoma (HCC) cells. However, the underlying mechanism has not been fully elucidated. The objective is to explore the molecular mechanism of PDGF-D-mediated EMT in drug resistance HCC cells. To achieve our goal, we used multiple approaches including Western blotting, real-time RT-PCR, wound healing assay, invasion assay, luciferase activity assay, transfection, and immunohistochemistry. We found that PDGF-D is highly expressed in gemcitabine-resistant (GR) HCC cells. Moreover, PDGF-D markedly inhibited miR-106a expression and subsequently upregulated Twist1 expression. Notably, PDGF-D expression was associated with miR-106a and Twist1 in HCC patients. Our findings provide a possible molecular mechanism for understanding GR chemoresistance in HCC cells. Therefore, inactivation of PDGF-D/Twist or activation of miR-106a could be a novel strategy for the treatment of HCC.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.