title: Pancreatic cancer derived exosomes regulate the expression of TLR4 in dendritic cells via miR-203.
abstract: MicroRNAs (miRNAs) are aberrant in many human tumors which can be transferred to immune cells by tumor-derived exosomes. Dendritic cells (DCs) play an important role in activation of immune response. However, the effect of tumor-derived exosomes on toll-like receptor (TLR) in DCs remains unclear. We investigated the influence of pancreatic cancer derived exosomes on TLR4, and downstream cytokines via miR-203. Our results showed that miR-203 expressed in panc-1 cells and exosomes, and upregulated in exosomes-treated DCs. TLR4 decreased after treatment of exosomes and miR-203 mimics, while increased in exosomes-treated DCs by miR-203 inhibitors. But the mRNA level of TLR4 was not significantly different between DCs and exosomes-treated DCs. Tumor necrosis factor-α (TNF-α) and interleukin-12 (IL-12) also decreased under treatment of exosomes and miR-203 mimics, both of which increased in exosomes-treated DCs by miR-203 inhibitors. Collectively, pancreatic cancer derived exosomes downregulate TLR4 and downstream cytokines in DCs via miR-203.
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Jionghuang
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Liangjing
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Ding
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China. Electronic address: zjulipingcao@163.com.
authors.forename: Liping
authors.initials: L
authors.lastname: Cao
mesh_terms: D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D055354:Exosomes / Q000276:immunology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: C546703:MIRN203 microRNA, human; D035683:MicroRNAs; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12
keywords: Dendritic cells; Exosomes; MicroRNAs; Pancreatic cancer; Toll-like receptor