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Abnormal Expression Of MiR-155 In Serum Of Breast Cancer Patients

Posted on:2012-04-10Degree:MasterType:Thesis
Country:ChinaCandidate:X Q WangFull Text:PDF
GTID:2154330335498859Subject:Oncology
Abstract/Summary:PDF Full Text Request
Micro-RNAs(miRNAs)are a new class of short sequences, non-protein-coding, small single-stranded RNAs with regulatory functions and of about 22 nucleotides in length, which are cleaved from single-stranded RNA precursors by the RNaseâ…¢Dicer. Mature miRNAs are known to negatively regulate gene expression or destroy the stability of genes via incomplete or complete matching with the 3'UTR of their target genes at the post-transcriptional level. They are involved in variety of physiological processes such as individual development, cell proliferation, apoptosis and differentiation, regulation of metabolism and stress response, even the occurrence of diseases,such as tumor formation. MiRNA involved in regulation of important biological processes of cancer cell, indirectly plays a oncogenes and anti-oncogenes function,and played a crucial role in occurrence and development of tumor, which makes the miRNA become a hot and difficult spot in oncology research.It has been demonstrated that circulating nucleic acid (CNA) which exists in body fluids including serum and blood plasma is closely related to cell metabolism in physiological and pathological condition. The detection and gene diagnosis of CNA has played a very important roie in the diagnosis of malignant tumors as a biomarker. MiRNAs are very stable in plasma and serum, free from RNA cleaving enzyme (RNases) remain stable in condition of long-term storage or repeated freezing and thawing,which shows that circulation miRNA from tumor can used as a biomarker.Objective:1. Extracting from serum miR-155 to detect the expression of miR-155 in serum between breast cancer patients and healthy controls.2. Combining with clinical data to analysis the relevance between miR-155 and clinical pathology data.3. To predict the target genes of miR-155 using bioinformatics methods and provide theoretical support for further research on mechanism of miR-155 in breast cancer occurrence development.4. In summary, this study hopes to find new molecular targets in treatment of breast cancer and new biomarkers for diagnosis and prognosis. Methods:1. Real-time quantitative PCR is used to detect the abnormal expression of miR-155 in the serum of 20 breast cancer patients compared withlO healthy controls.2. Combining with clinical data to statistical analysis3. Different bioinformatic ways are used to predict the target genes of miR-155.Results:1. There is significantly difference in miR-155 between breast cancer patients combined and healthy controls (p<0.05),and miR-155 is up-regulated in serum of breast cancer.2. There is a statistical difference in miR-155 in serum of breast cancer patients in clinical stage, molecular subtypes, Ki-67 and P53 between different subgroups(p<0.05), the relative expression:stageâ…¢>stageâ…¡> stageâ… , triple negative type HER-2 (+) type> luminalB type> luminalA type, Ki-67(+)> Ki-67(-), P53(-)> P53(+).There is no statistical difference in miR-155 in serum of breast cancer patients in age, histological grade, between different subgroups (p>0.05). In the Ki-67 (+) group, There is a statistical difference in miR-155 in serum of breast cancer patients in different molecular subtypes, lymph nodes condition between different subgroups(p<0.05),the relative express:HER-2> luminalB> luminalA,LN(+)>LN(-).3. Searching miR-155 sequence by miRBase software, predicting target genes of miR-155 by Pictar, Targetscan, and miRanda Micro-RNA predicting software.There are 92 target genes predicted by at least two bioinformatic ways, most of the genes are involved in cell cycles, cell proliferation, differentiation, apoptosis> signal transduction and so on.Conclusions:1. MiR-155 is up-regulated in breast cancer in serum of breast cancer patients compared with healthy controls. MiR-155 may become a novel class of biomarkers for early diagnosis of breast cancer.2. MiR155 in serum of breast cancer is relevant with clinical stage, molecularsubtypes, the condition of Ki-67, P53, The relative expression of late clinical stage, negative hormone receptor, Ki-67 (+), p53(-) is higher; otherwise lower. 3. Bioinformatic predicts miR-155 might be lead to changes in the biological characteristics of breast cancer cells by regulating the translation of downstream target genes...
Keywords/Search Tags:Breast Cancer, Serum, micro-RNA, Target Gene, Biomarker
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