MicroRNA 483-3p suppresses the expression of DPC4/Smad4 in pancreatic cancer.
Both deregulation of tumor-suppressor genes and misexpression of microRNAs (miRNAs) have been implicated in the development of pancreatic cancer, but their relationship during this process remains less clear. Here, we report that the expression of miR-483-3p is strongly enhanced in pancreatic cancer tissues compared to side normal tissues using a miRNA-array differential analysis. Furthermore, DPC4/Smad4 is identified as a target of miR-483-3p and their expression levels are inversely correlated in human clinical specimens. Ectopic expression of miR-483-3p significantly represses DPC4/Smad4 protein levels in pancreatic cancer cell lines, and simultaneously promotes cell proliferation and colony formation in vitro. Our findings identify miR-483-3p as a potent regulator of DPC4/Smad4, which may provide a novel therapeutic strategy for the treatment of DPC4/Smad4-driven pancreatic cancer.
Department of Pancreatic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
Jun
J
Hao
Shuyu
S
Zhang
Yingqi
Y
Zhou
Xiangui
X
Hu
Chenghao
C
Shao
D020413:3' Untranslated Regions / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051901:Smad4 Protein / Q000235:genetics*; D014162:Transfection; D014410:Tumor Stem Cell Assay
D020413:3' Untranslated Regions; C548912:MIRN483 microRNA, human; D035683:MicroRNAs; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D008156:Luciferases