Clinical Significance of Upregulation of mir-196a-5p in Gastric Cancer and Enriched KEGG Pathway Analysis of Target Genes


Background: miRNAs are relatively recently discovered cancer biomarkers which have important implicationsfor cancer early diagnosis, treatment and estimation of prognosis. Here we focussed on expression of mir-196a-5pin gastric cancer tissues and cell lines so as to analyse its significance for clinicopathologic characteristics andgenerate enriched KEGG pathways clustered by target genes for exploring its potential roles as a biomarker ingastric cancer. Materials and
Methods: The expression of mir-196a-5p in poorly, moderate and well differentiatedgastric cancer cell lines compared with GES-1 was detected by RT-qPCR, and the expression of mir-196a-5pin gastric cancer tissues comparing with adjacent non cancer tissues of 58 cases were also assessed by RTqPCR.Subsequently, an analysis of clinical significance of mir-196a-5p in gastric cancer and enriched KEGGpathways was executed based on the miRWalk prediction database combined with bioinformatics tools DAVID6.7 and Mirfocus 3.0.
Results: RT-qPCR showed that mir-196a-5p was up-regulated in 6 poorly and moderatedifferentiated gastric cancer cell lines SGC-7901, MKN-45, MKN-28, MGC-803, BGC-823, HGC-27 comparedwith GES-1, but down-regulated in the highly differentiated gastric cancer cell line AGS. Clinical data indicatedmir-196a-5p to beup-regulated in gastric cancer tissues (47/58). Overexpression of mir-196a-5p was associatedwith more extensive degree of lymph node metastasis and clinical stage (P < 0.05; x2 test). Enriched KEGGpathway analyses of predicted and validated targets in miRWalk combined with DAVID 6.7 and Mirfocus3.0 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, andenriched KEGG pathway analyses showed that targeted genes regulated by mir-196a-5p may contribute totumorgenesis, suggesting roles as an oncogenic miRNA biomarker in gastric cancer.