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The PDGF-D/miR-106a/Twist1 pathway orchestrates epithelial-mesenchymal transition in gemcitabine resistance hepatoma cells

2015; Impact Journals LLC; Volume: 6; Issue: 9 Linguagem: Inglês

10.18632/oncotarget.3193

1949-2553

Rui Wang, Yumei Li, Yueyue Hou, Qingling Yang, Sulian Chen, Xi Wang, Zishu Wang, Yan Yang, Changjie Chen, Zhiwei Wang, Qiong Wu,

Cancer, Hypoxia, and Metabolism

// Rui Wang 1 , Yumei Li 1 , Yueyue Hou 1 , Qingling Yang 2 , Sulian Chen 2 , Xi Wang 3 , Zishu Wang 1 , Yan Yang 1 , Changjie Chen 2 , Zhiwei Wang 4 , Qiong Wu 1 1 Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China 2 Department of Biochemistry and Molecular Biology, Bengbu Medical College, Anhui, China 3 Department of Oncology, The 117th Hospital of PLA, Hangzhou, China 4 The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University, Suzhou, China Correspondence to: Qiong Wu, e-mail: qiongwu68@outlook.com Zhiwei Wang, e-mail: zwang6@bidmc.harvard.edu Keywords: Hepatocellular carcinoma, EMT, PDGF-D, miR-106a, Twist Received: December 16, 2014 Accepted: January 23, 2015 Published: February 11, 2015 ABSTRACT 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.