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The Relationship Of MiR-155 And CerbB-2 In Breast Cancer Cells; The Influence Of Chemotherapeutics To The Expression Level Of MiR-155

Posted on:2010-05-30Degree:MasterType:Thesis
Country:ChinaCandidate:T H HuFull Text:PDF
GTID:2144360275992099Subject:Surgery
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Background:MicroRNAs(miRNAs) are an abundant class of 20-22 nucleotide small non-coding,evolutionarily conserved RNA molecules that negatively regulate gene expression through sequence-specific translational repression and/or degradation of cognate mRNA.MicroRNAs have been implicated in control of many fundamental cellular and physiological processes.Mounting evidence indicates that their aberrant expression might be involved in human cancers,and they might be useful for diagnosis and therapeutics in cancer.Our former study found that the expression of miR-155 in tumor tissue was significantly elevated in comparison with paired normal breast tissue,and its expression level had significant correlation with CerbB-2 expression.Moreover,we found,to patients who received neo-adjuvant chemotherapy, miR-155 level in tumor tissue was lower,implicating that chemotherapeutics might influence the expression of mir-155.The results indicates miRNAs might be used as useful new biomarkers for early diagnosis and therapeutics in breast cancer.Methods:To investigate the effect of miR-155 on the expression of CerbB-2,we used miR-155 expression construct or miR-155 mimics(pre-miR-155) to up-regulate,or used miR-155 antisense(miR-155 inhibitor) to down-regulate miR-155 level in CerbB-2 positive human breast cancer cells MCF-7.Total RNA isolation was done with TRIzol according to the instructions of manufacturer,and quantitative Real-Time PCR was used to quantify the expression level of CerbB-2.To study the effects of chemotherapeutics drugs on mir-155 expression,we used different chemotherapeutics and combined chemotherapy drugs treating human breast cancer MDA-231 cells,and assayed the expression levels of miR-155 using TaqMan miRNA assay kits following the drug treatments.Results:The expression level of CerbB-2 was elevated when up-regulation of miR-155,and was reduced when down-regulation of miR-155 in MCF-7 cells.In MDA-231 cells,each drug and combine chemotherapy could down-regulate the expression of miR-155 significantly,which informed us that chemotherapeutics could inhibit miR-155 expression.Conclusion:In breast cancer cells MCF-7,the expression of CerbB-2 is regulated by miR-155.All chemotherapeutics could inhibit the expression of miR-155 in MDA-231 cells,and the drug inhibition is concentration-dependent.
Keywords/Search Tags:microRNA(miRNA), miR-155, breast cancer, CerbB-2, chemotherapeutics
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