title: MicroRNA 421 suppresses DPC4/Smad4 in pancreatic cancer.
abstract: MicroRNAs (miRNAs) have emerged as important regulators in the development of pancreatic cancer and may be a valuable therapeutic application. DPC4/Smad4 is a critical tumor suppressor involved in the progression of pancreatic cancer, but few studies have been conducted to determine its relationship with miRNAs. In this study, we identify miR-421 as a potential regulator of DPC4/Smad4. We find that in human clinical specimens of pancreatic cancer miR-421 is aberrantly upregulated while DPC4/Smad4 is strongly repressed, and their levels of expression are inversely correlated. Moreover, ectopic expression of miR-421 significantly decreases DPC4/Smad4 protein level in pancreatic cancer cell lines and simultaneously promotes cell proliferation and colony formation in vitro. Our findings identify miR-421 as a potent regulator of DPC4/Smad4, which may provide a novel therapeutic strategy for treatment of DPC4/Smad4-driven pancreatic cancer.
authors.affiliation: Department of Pancreatic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hao
authors.forename: Shuyu
authors.initials: S
authors.lastname: Zhang
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Cong
authors.initials: C
authors.lastname: Liu
authors.forename: Xiangui
authors.initials: X
authors.lastname: Hu
authors.forename: Chenghao
authors.initials: C
authors.lastname: Shao
mesh_terms: D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D051901:Smad4 Protein / Q000235:genetics*
chemical_list: C547665:MIRN421 microRNA, human; D035683:MicroRNAs; C497796:SMAD4 protein, human; D051901:Smad4 Protein