title: Quantitative proteomic analysis of the metastasis-inhibitory mechanism of miR-193a-3p in non-small cell lung cancer.
abstract: BACKGROUND
  microRNAs can repress the expression of target genes by destabilizing their mRNAs or by inhibiting their translation. Our previous findings suggested that miR-193a-3p inhibited the progression of NSCLC both in vitro and in vivo. However, the biological processes and molecular pathways through which this miRNA exerts its positive effects are unknown.
  
  
  METHODS
  To explore the molecular mechanisms by which miR-193a-3p inhibited NSCLC metastasis, we investigated the changes in the protein profile of SPC-A-1sci (highly metastatic) cells in response to the up-regulation of miR-193a-3p expression using a proteomics approach (iTRAQ combined with NanoLC-MS/MS). Changes in the profiles of the expressed proteins were verified using western blotting and were analyzed using the DAVID and STRING programs.
  
  
  RESULTS
  In the two replicated experiments, 4962/4946 proteins were identified, and the levels of expression of 4923/4902 proteins were quantified. In total, 112 of these proteins were differentially expressed. Among them, the up-regulated levels of expression of two of the 62 proteins with up-regulated expression (PPP2R2A and GSN) and the down-regulated levels of expression four of the 50 proteins with down-regulated expression (LMNB2, UHRF1, G3BP1, and HNRNPU) were verified using western blotting. The bioinformatics analysis revealed the interactions and signaling networks of these differentially expressed proteins.
  
  
  CONCLUSIONS
  miR-193a-3p inhibited the metastasis of lung cancer cells by deregulating the expression of tumor-related proteins. These findings may improve the understanding of the molecular mechanisms underlying the metastatic-inhibitory effect of miR-193a-3p on lung cancer cells.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.forename: Mingxia
authors.initials: M
authors.lastname: Yan
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.forename: Haiyan
authors.initials: H
authors.lastname: Ge
authors.forename: Hechun
authors.initials: H
authors.lastname: Lin
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Qin
authors.initials: Q
authors.lastname: Geng
authors.forename: Miaoxin
authors.initials: M
authors.lastname: Zhu
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Xianghuo
authors.initials: X
authors.lastname: He
authors.forename: Ming
authors.initials: M
authors.lastname: Yao
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D016000:Cluster Analysis; D016208:Databases, Factual; D015536:Down-Regulation; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D060066:Protein Interaction Maps; D040901:Proteomics; D053719:Tandem Mass Spectrometry; D015854:Up-Regulation
chemical_list: C546818:MIRN193 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense