Aberrant elevated microRNA-146a in dendritic cells (DC) induced by human pancreatic cancer cell line BxPC-3-conditioned medium inhibits DC maturation and activation.
It has been shown that the function of dendritic cell (DC) is suppressed in pancreatic cancer patients; however, the detailed mechanism involved in it remains unclear. Here, we used medium conditioned by a highly metastatic human pancreatic cancer cell line BxPC-3 [BxPC-3-conditioned medium (BxCM)] to culture human CD14+ monocyte-derived DCs in vitro. Both DC differentiation and antigen presentation function were inhibited by BxCM. The microRNA-146a (miRNA-146a) expression is aberrantly up-regulated in BxCM-treated DCs. In addition, inhibition of aberrant miRNA-146a expression partly rescues the BxCM-induced defects in differentiation and function of DCs, which may be through regulation of Smad4 expression. Taken together, our findings indicate that aberrant miRNA-146a expression is one of main factors responsible for inhibition of DC maturation and antigen presentation function, and this inhibitory effect on DCs may be due to the repression of Smad4 mediated signal pathway by BxCM.
Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, No. 222, Zhongshan Road, Dalian, 116011, People's Republic of China.
Jian
J
Du
Jingwen
J
Wang
Guang
G
Tan
Zhengang
Z
Cai
Lu
L
Zhang
Bo
B
Tang
Zhongyu
Z
Wang
D002454:Cell Differentiation; D045744:Cell Line, Tumor; D019295:Computational Biology; D017077:Culture Media, Conditioned; D003713:Dendritic Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008213:Lymphocyte Activation; D035683:MicroRNAs / Q000032:analysis / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D051901:Smad4 Protein / Q000032:analysis / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology
D017077:Culture Media, Conditioned; D018950:Lipopolysaccharide Receptors; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; C497796:SMAD4 protein, human; D051901:Smad4 Protein