The Abnormal Expression Of MiRNA-200a In Gastric Cancer And Target Gene Prediction

Objective:Gastric cancer is a malignant tumor derived from gastricepithelium which is higher in morbidity and mortality.China appears to haveboth relatively high incidence rate and mortality rate of gastric cancer in theworld.Although currently treatments including surgery,radiotherapy,chemotherapy and the comprehensive treatment such as biological therapy, butthe effect of the treatment is still not ideal, and the five years survival rate ofgastric cancer is so low.Multisteps led the gene alteration are responsible forthe development of cancer.It is the result of the accumulation of genealteration involving a variety of oncogenes and tumor suppressorgenes.Clarifying the underlying molecular mechanism,not only help toelucidate the pathogenesis of gastric cancer,but also to assist in tumortreatment and prognosis.Studies have shown that a class of21~25ntsingle-stranded non-coding microRNA play important roles in thedevelopment of tumors.Plenty of studies have demonstrated that miRNAscould contribute to most,if not all,basic biological proeesses,such asdevelopment,cells proliferation,migration and invasion.Many of studies makeit clear that miRNAs are associated with lots of diseases,includin geancers.Asone of the reasons, microRNA have earned more and more attention.SomemiRNAs that are assoeiated with gastric cancer have been identified to datethe role of many of them in stomach tumorigenesis and the underiyingmechanism remain to be determined. MiRNA-200a is expressed in manytissues,but the relationship between miRNA-200a and gastric carcinoma ispoorly understood.In this study,we screened differentially expressed miR-200abetween gastric tumor tissue and adjacent non-tumor tissue throughquantitative Real-time PCR and explore the significance between theexpression changes and clinicopathologic factors. It is clear that miRNA-200a may funetion as potential oncogenes or tumor suppressors,and alteration inmiRNA-200a expression may play a critical role in gastric cancer.Identifieation of cancer speeiflc miRNA-200a and theirtargets is critical forunderstanding their roles in carcinogenesis and may be important for definingnovel therapeutic targets.Potential target genes of miR-200a were predicted byseveral bioinformatic programs,and their association with gastric pathogenesiswas preliminarily investigated.Methods:1Tissue samples were obtained from27patients undergoing gastrectomyfor gastric cancer. The expression of miR-200a was analyzed using Real-timePCR.2Then, we investigated the association of clinical and pathologicalcharacteristics of cancer samples with miR-200a expression throughindependent sample t test and one-way ANOVA.3Potential target genes of miR-200a were predicted by severalbioinformatic programs. The GO classification of common target genes, andits significant screening, further narrowing the range of target gene.Results:1Real-time PCR analysis displayed the decrease of miR-200a wasclearly The results showed that22cases (81%) the expression level ofmiRNA-200a in cancer tissues was significantly lower than that of normaltissues,5cases (29%) was higher than that of normal tissues adjacent tocancer. Relative expression value of RQ was0.33±0.01in gastric cancertissues and corresponding adjacent normal tissues,0.78±0.15, the resultsshowed that miRNA-200a expression in gastric cancer tissues wassignificantly down-regulated, with statistical significance (P <0.05)2However,except intravascular cancer embolus we failed to observe anyassociation of miR-200a expression with clinical and pathological parametersof gastric cancer.3Using bioinformatic algorithms,we predicted KHDRBS2, GNB1,HMGB1,NOVA1,PAFAH1B1,PELI1,HCN4,NAMPT,DLC1,RAB10,TCERG1 ,SSX2IP,HTR2C,HTR3C,HTR4C,NOTCH2,CRLF3,GULP1,YPEL5,POU4F2,C2orf42,PAG1,DPP10,SFRS1,STC1,THBS1,UBE3A,WHSC1,YY1,SYNGR1,VAMP3,AKAP6,PAOLG,HNRPDL,CX3CR1,ARMC1,SFRS6,C1orf25aspotential targets of miR-200a involved in gastric carcinogenesis. The targetgenes were significant screening, prompting some target genes involved insignal transduction, protein phosphorylation, cell proliferation, migration,apoptosis.Conclusion:1miRNA-200a was down-regulated in gastric tumor tissue comparedwith adjacent non-tumor tissue,suggesting that down-regulation ofmiRNA-200a is associated with the pathogenesis of stomach cancer.2There was significant correlation between miRNA-200a expression andtumor thrombus This suggest miRNA-200-a play a guiding role in theinvasion of gastric cancer.3Bioinformatics analysis result shows that the miRNA-200a byregulating and controlling gene expression in signal transduction, proteinphosphorylatio-n,cell proliferation, migration, apoptosis. However, therelevance between miR-200a and gastric cance also need further research.