title: MicroRNA-301a-3p promotes pancreatic cancer progression via negative regulation of SMAD4.
abstract: BACKGROUND
  Aim to determine the clinicopathological and prognostic role of miR-301a-3p in pancreatic ductal adenocarcinoma(PDAC), to investigate the biological mechanism of miR-301a-3p in vitro and in vivo.
  
  
  METHODS
  By tissue microarray analysis, we studied miR-301a-3p expression in PDAC patients and its clinicopathological correlations as well as prognostic significance. qRT-PCR was used to test miR-301a-3p expression in PDAC tissues and cell lines. Functional experiments including in vitro and in vivo were performed.
  
  
  RESULTS
  Significantly higher expression of miR-301a-3p were found in PDAC patients with lymph node metastasis and advanced pathological stages and identified as an independent prognostic factor for worse survival. In PDAC samples and cell lines, miR-301a-3p was significantly up-regulated compared with matched non-tumor tissues and normal pancreatic ductal cells, respectively. Overexpression of miR-301a-3p enhanced PDAC cells colony, invasion and migration abilities in vitro as well as tumorigenicity in vivo. Furthermore, SMAD4 was identified as a target gene of miR-301a-3p by cell as well as mice xenograft experiments. In PDAC tissue microarray, a significantly inverse correlation between miR-301a-3p ISH scores and SMAD4 IHC scores were observed in both tumor and corresponding non-tumor tissues.
  
  
  CONCLUSIONS
  MiR-301a-3p functions as a novel oncogene in PDAC and the oncogenic activity may involve its inhibition of the target gene SMAD4.
authors.affiliation: Department of General Surgery, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Xia
authors.affiliation: Department of General Surgery, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, China.
authors.forename: Kundong
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Cen
authors.affiliation: Department of General Surgery, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of General Surgery, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of General Surgery, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, China.
authors.forename: Kejian
authors.initials: K
authors.lastname: Huang
authors.affiliation: Department of General Surgery, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis and National Ministry of Education, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, China.
authors.forename: Zhengjun
authors.initials: Z
authors.lastname: Qiu
mesh_terms: D000368:Aged; D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D016577:Pancreaticoduodenectomy; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D051901:Smad4 Protein / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: C550735:MIRN301A microRNA, human; D035683:MicroRNAs; C497796:SMAD4 protein, human; D051901:Smad4 Protein
keywords: SMAD4; miR-301a-3p; pancreatic ductal adenocarcinoma; prognosis; xenograft tumor