title: Clinical significance of upregulation of mir-196a-5p in gastric cancer and enriched KEGG pathway analysis of target genes.
abstract: BACKGROUND
  miRNAs are relatively recently discovered cancer biomarkers which have important implications for cancer early diagnosis, treatment and estimation of prognosis. Here we focussed on expression of mir-196a-5p in gastric cancer tissues and cell lines so as to analyse its significance for clinicopathologic characteristics and generate enriched KEGG pathways clustered by target genes for exploring its potential roles as a biomarker in gastric cancer.
  
  
  METHODS
  The expression of mir-196a-5p in poorly, moderate and well differentiated gastric cancer cell lines compared with GES-1 was detected by RT-qPCR, and the expression of mir-196a-5p in gastric cancer tissues comparing with adjacent non cancer tissues of 58 cases were also assessed by RT- qPCR. Subsequently, an analysis of clinical significance of mir-196a-5p in gastric cancer and enriched KEGG pathways was executed based on the miRWalk prediction database combined with bioinformatics tools DAVID 6.7 and Mirfocus 3.0.
  
  
  RESULTS
  RT-qPCR showed that mir-196a-5p was up-regulated in 6 poorly and moderate differentiated gastric cancer cell lines SGC-7901, MKN-45, MKN-28, MGC-803, BGC-823, HGC-27 compared with GES-1, but down-regulated in the highly differentiated gastric cancer cell line AGS. Clinical data indicated mir-196a-5p to beup-regulated in gastric cancer tissues (47/58). Overexpression of mir-196a-5p was associated with more extensive degree of lymph node metastasis and clinical stage (P <0.05; x2 test). Enriched KEGG pathway analyses of predicted and validated targets in miRWalk combined with DAVID 6.7 and Mirfocus 3.0 showed that the targeted genes regulated by mir-196a-5p were involved in malignancy associated biology.
  
  
  CONCLUSIONS
  Overexpression of mir-196a-5p is associated with lymph node metastasis and clinical stage, and enriched KEGG pathway analyses showed that targeted genes regulated by mir-196a-5p may contribute to tumorgenesis, suggesting roles as an oncogenic miRNA biomarker in gastric cancer.
authors.affiliation: Department of Clinical Testing Teaching and Research, School of Medical Technology, Gansu Traditional Chinese Medical University, Lanzhou, China E-mail : wu.hy@126.com.
authors.forename: Hai-Long
authors.initials: HL
authors.lastname: Li
authors.forename: Shou-Pin
authors.initials: SP
authors.lastname: Xie
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Yang
authors.forename: Ying-Xia
authors.initials: YX
authors.lastname: Cheng
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Da-Long
authors.initials: DL
authors.lastname: Liu
authors.forename: Zhao-Feng
authors.initials: ZF
authors.lastname: Chen
authors.forename: Yong-Ning
authors.initials: YN
authors.lastname: Zhou
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Wu
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D004734:Energy Metabolism / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C542543:MIRN196 microRNA, human; D035683:MicroRNAs