title: The PDGF-D/miR-106a/Twist1 pathway orchestrates epithelial-mesenchymal transition in gemcitabine resistance hepatoma cells.
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.
authors.affiliation: Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
authors.forename: Yueyue
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Department of Biochemistry and Molecular Biology, Bengbu Medical College, Anhui, China.
authors.forename: Qingling
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, Bengbu Medical College, Anhui, China.
authors.forename: Sulian
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Oncology, The 117th Hospital of PLA, Hangzhou, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
authors.forename: Zishu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, Bengbu Medical College, Anhui, China.
authors.forename: Changjie
authors.initials: C
authors.lastname: Chen
authors.affiliation: The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University, Suzhou, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
mesh_terms: D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism*; D008222:Lymphokines / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000378:metabolism*; D014945:Wound Healing; D000093542:Gemcitabine
chemical_list: D008222:Lymphokines; C542541:MIRN106 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; C427493:PDGFD protein, human; D010982:Platelet-Derived Growth Factor; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: EMT; PDGF-D; Twist; hepatocellular carcinoma; miR-106a