title: MiR-371-5p facilitates pancreatic cancer cell proliferation and decreases patient survival.
abstract: BACKGROUND
  microRNAs (miRNAs) play a critical role in tumorigenesis, either as a tumor suppressor or as an oncogenic miRNA, depending on different tumor types. To date, scientists have obtained a substantial amount of knowledge with regard to miRNAs in pancreatic cancer. However, the expression and function of miR-371-5p in pancreatic cancer has not been clearly elucidated. The aim of this study was to investigate the roles of miR-371-5p in pancreatic cancer and its association with the survival of patients with pancreatic cancer.
  
  
  METHODS
  The expression of miR-371-5p was examined in pancreatic duct adenocarcinoma (PDAC) and their adjacent normal pancreatic tissues (ANPT) or in pancreatic cancer cell lines by qRT-PCR. The association of miR-371-5p expression with overall survival was determined. The proliferation and apoptosis of SW-1990 and Panc-1 cells, transfected with miR-371-5p mimics or inhibitor, were assessed using MTT assay and flow cytometry, respectively. The tumorigenicity was evaluated via mice xenograft experiments. miR-371-5p promoter interactions were analyzed by chromatin immunoprecipitation assays (ChIP). Protein expression was analyzed by Western blot.
  
  
  RESULTS
  The expression level of miR-371-5p was dramatically upregulated in clinical PDAC tissues compared with ANPT. Patients with high miR-371-5p expression had a significantly shorter survival than those with low miR-371-5p expression. The in vitro and in vivo assays showed that overexpression of miR-371-5p resulted in cell proliferation and increased tumor growth, which was associated with inhibitor of growth 1 (ING1) downregulation. Interestingly, we also found that ING1, in turn, inhibited expression of miR-371-5p in the promoter region.
  
  
  CONCLUSIONS
  our study demonstrates a novel ING1-miR-371-5p regulatory feedback loop, which may have a critical role in PDAC. Thus miR-371-5p can prove to be a novel prognostic factor and therapeutic target for pancreatic cancer treatment.
authors.affiliation: Department of General Surgery, Affiliated Baoan Hospital of Southern Medical University, Shenzhen, China.
authors.forename: De
authors.initials: D
authors.lastname: He
authors.affiliation: Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China.
authors.forename: Huilai
authors.initials: H
authors.lastname: Miao
authors.affiliation: Department of General Surgery, Affiliated Baoan Hospital of Southern Medical University, Shenzhen, China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of General Surgery, Affiliated Baoan Hospital of Southern Medical University, Shenzhen, China.
authors.forename: Longhui
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Department of General Surgery, Affiliated Baoan Hospital of Southern Medical University, Shenzhen, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Affiliated Baoan Hospital of Southern Medical University, Shenzhen, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Xiang
authors.affiliation: Department of Medicine, College of Clinical Science of China, Three Gorges University, Yichang, Hubei, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Robert Wood Johnson Medical School University Hospital, Rutgers Unversity, New Brunswick, New Jersey, United States of America.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000401:mortality* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology*; D011401:Promoter Regions, Genetic; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; C554834:MIRN371 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins