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The Expression Of MirRNA-429in Gastric Cancer And The Bioinformatics Of A Preliminary Study

Posted on:2014-02-26Degree:MasterType:Thesis
Country:ChinaCandidate:Y X ZhangFull Text:PDF
GTID:2234330398493827Subject:Oncology
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Objective: China is country with high incidence rates of gastric cancer.Due to the screening of gastric cancer not gaining popularity and attention, themajority of patients with gastric cancer is in the late stage, and thus delayedthe best treatment time. Although diagnostic and treatment technology ofgastric cancer has been improving, the prognosis is still not satisfactory,five-year survival rate only30percent. Therefore, the study to thedevelopment and transfer mechanism of gastric cancer is critical.microRNA(miRNA) are a novel class of endogenous small,non-coding RNAthat exert their posttranscriptional regulatory effects by targeting3’untranslated region(3’-UTR)of corresponding mRNAs. It plays similarfunction with oncogenes or tumor suppressor genes, and plays an importantrole in the occurrence and development of the tumor. At present, the stduy ofmiRNA in gastric cancer are constant deepening at home and abroad, whichwill play an important role in the gene diagnosis and treatment of gastriccancer. Investigate the differential expression of miRNA-429in patients withgastric cancer tissues and paired adjacent normal tissue, and study itsrelevance with clinicopathological parameters of gastric cancer. Usingbioinformatics methods to predict the target genes of miRNA-429and theyplay a biological function, then provide theoretical support for further researchon mechanism of miRNA-429in gastric cancer of occurrence anddevelopment.Methods:1Collected27pairs of gastric cancer tissues and paired adjacentnontumorous tissues, drawn in surgery, immediately placed in liquid nitrogen,and then transferred to-80℃long-term preservation. Be drawn from thepatients before surgery not undergone radiotherapy and chemotherapy. TNM stage as the standard AJCC (American Joint Committeeon Cancer) seventhedition of the TNM pathological staging.2Real-time quantitative PCR is used to detect the expression ofmiRNA-429in the27pairs of gastric cancerous and paired non-canceroustissues. Using CT method indicates the relative expression level ofmiRNA-429.3Application of statistical methods to analysis of the relationshipbetween the expression level of miRNA-429and the27pairs of gastricclinical and pathological features.4Adopt the miRBase database to retrieve basic information ofmiRNA-429, using the miRanda, Targetscan and Pictar three databasesmiRNA-429target gene prediction, screened out at two or more software canbe predicted to gene as a possible target genes.5GO analysis of potential target genes of miRNA-429, note target genethe biological process, and summarize the biological function of the targetgene mainly play.Results:1Real time-PCR test results show: miRNA-429in27gastric carcinomaand paraneoplastic paired normal tissue relative expression levels of(0.36±0.52)and (0.62±0.66) respectively, paired in adjacent normal tissueexpression levels gastric tissue1.722, difference was statisticallysignificant(P<0.05), MiR-429were down-regulated in gastric cancer tissues.2Statistical method analysis show: miRNA-429in no intravascularcancerembolus expression amount of intravascular cancerembolus4.744times(p<0.05), and amount of expression in histological moderately differentiatedgroup is3.125times low differentiation group(p<0.05).Suggests that thelower the level expression miRNA-429, the higher lymphatic been infringedchance, and the lower the degree of histological, the lower expression levelmiRNA-429. It shows that low expression of miRNA-429has significancerelevance with lymphatic invasion and histological grade(p<0.05).Withoutage, gender, tumor size, depth of invasion, lymph node metastasis and clinical stage(p>0.05).3miRNA-429target gene screening results show: In these three themiRanda, Targetscan and Pictar database, two or more of the software can bepredicted from the target gene is a total of87, including MED13, ZEB1, NPC1,PKD1, CRH, IHPK1, GOLGA8A, KLF10, REV1L, GDI2, CDR2, EDNRA,HLF, LRP1, ZEB2etc.4Target genes GO analysis results show that:87target genes ofmiRNA-429main functions include biological process, such as invasion anddiversion, asmesenchymal cell differentiation, mesenchymal cell development,tube development, cytoskeleton organization, chordate embryonicdevelopment, embryonic development ending in birth or egg hatching,negative regulation of cellular biosynthetic process and neural crest celldifferentiation. ZEB1, ZEB2, PKD1, GDI2, LRP1may be a potential targetgenes for miRNA-429regulating gastric cancer invasion and metastasis.Conclusion:1miRNA-429was down-regulated expression in gastric cancer tissues,suggesting that miRNA-429may play a similar role of the tumor suppressorgene in gastric cancer.2miRNA-429expression with lymphatic invasion, and the degree ofhistological was negatively correlate and has no relevance with the patient’sage, gender, tumor size, depth of invasion, lymph node metastasis and clinicalstage. It suggests that miRNA-429down-regulated expression may suppressinvasion and metastasis of gastric inhibitory, and may play a guiding role inthe prognosis of gastric cancer.3Using bioinformatics analyze87target genes of miRNA-429, combinedwith its biological functions show that: miRNA-429expression in gastricdisorder, May regulate the expression of a series of target genes through,resulting in the changes of gastric cancer cells in a variety of biologicalcharacteristics.
Keywords/Search Tags:Gastric cancer, miRNA-429, Clinicopathologicalcharacteristics, Target gene, Bioinformatics
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