title: MiR-4782-3p inhibited non-small cell lung cancer growth via USP14.
abstract: BACKGROUND
  Lung cancer is the leading cause of cancer-related mortality worldwide, with near 1.4 million deaths each year. NSCLC accounts for nearly 85% of all case of lung cancer. MiRNAs play important roles in regulation of gene expression at the post-transcriptional level. MiRNAs profiles may predict prognosis and disease recurrence in early-stage NSCLC. Our previous study proved that over-expression of ubiquitin specific peptidase 14 (USP14), a deubiquitinating enzyme, was associated with favorable prognosis in NSCLC patients and promoted tumor cells proliferation. Here, we tried to identify which miRNAs targeted USP14, and the roles of these miRNAs in NSCLC.
  
  
  METHODS
  MiR-4782-3p and its potential targeted genes were identified by bioinformatics algorithm. Dual luciferase reporter assay system was used to analyze the interaction between miR-4782-3p and targeted genes. Cell proliferation was assayed by MTT and BdU assay. MiRNAs and mRNA expression were assayed by qRT-PCR. USP14 protein level was assayed by Western blot. The role of miR-4782-3p in patients survival was revealed by Kaplan-Meier plot of overall survival.
  
  
  RESULTS
  Up-expression of miR-4782-3p in NSCLC cells decreased the USP14 expression. Down-expression of miR-4782-3p increased USP14 expression. In NSCLC specimen, Negative correlation between USP14 mRNA level and miR-4782-3p level was identified. Higher miR-4782-3p expression is associated with longer survival. USP14, ZEB2, XIAP overexpression reversed the inhibitory effect of miR-4782-3p.
  
  
  CONCLUSIONS
  High expression of miR-4782-3p was associated with favorable prognosis in NSCLC patients. MiR-4782-3p inhibited cell proliferation in NSCLC by targeting USP14, ZEB2 and XIAP.
authors.affiliation: Department of Respiratory Medicine, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wu
authors.forename: Chaoxiong
authors.initials: C
authors.lastname: Zhang
authors.forename: Chong
authors.initials: C
authors.lastname: Bai
authors.forename: Yi Pang
authors.initials: YP
authors.lastname: Han
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality; D049109:Cell Proliferation; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D012334:RNA, Neoplasm / Q000096:biosynthesis*; D012097:Repressor Proteins / Q000096:biosynthesis; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D043222:Ubiquitin Thiolesterase / Q000096:biosynthesis*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000096:biosynthesis; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D018398:Homeodomain Proteins; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D012097:Repressor Proteins; C509299:USP14 protein, human; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D043222:Ubiquitin Thiolesterase