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Study On Expression Of Hsa-miR-20a In Human Glioma Tissues And Its Effect On The Proliferation Of Human Glioma Cells

Posted on:2013-03-16Degree:MasterType:Thesis
Country:ChinaCandidate:J Z ZhangFull Text:PDF
GTID:2234330371483471Subject:Surgery
Abstract/Summary:PDF Full Text Request
Gliomas are the most common form of primary brain tumors and are associated with apoor clinical outcome. The molecular mechanisms that contribute to gliomagenesis havebecome increasingly clear in recent years, yet much remains to be learned. This is particularlytrue for the role of microRNAs in gliomagenesis, as an appreciation for the significance ofaberrant miRNA expression in human cancer has only emerged in the last few years. It is nowevident that microRNAs regulate a wide variety of tumorigenic processes including cellularproliferation, differentiation, angiogenesis, invasion, and apoptosis.MicroRNAs (miRNAs, miRs) are small, noncoding RNA molecules, about22nucleotides in length, that regulate gene expression posttranscriptionally, which usuallyrepress gene expression by binding at the3’UTR region of target gene. Emerging evidenceindicates that miRNAs play an important role in the development of human cancers, withtheir deregulation resulting in altered activity of downstream tumor suppressors, oncogenesand other signaling molecules. Recent years have seen considerable progress in miRNAresearch in brain tumors, particularly in glioblastomas, providing novel insights into thepathogenesis of these malignant lesions. Expression profiling has unveiled miRNA signaturesthat not only distinguish brain tumors from normal tissues, but can also differentiatehistotypes or molecular subtypes with altered genetic pathways. Moreover, specific miRNAsubsets may have potential diagnostic and prognostic values in some brain tumors. Severalderegulated miRNAs uncovered in glioblastomas have their gene targets and the associatedgenetic pathways identified.and the therapeutic potential ofmicroRNAs to improve outcomfor glioma patients.hsa-miR-20a, a member of the mir-17–92cluster, modulates the translation of the E2F2and E2F3mRNAs via binding sites in their3,-untranslated region. We also found that the endogenous E2F1, E2F2, and E2F3directly bind the promoter of the mir-17–92clusteractivating its transcription, suggesting an autoregulatory feedback loop between E2F factorsand miRNAs from the mir-17–92cluster. Our data also point toward an antiapoptotic rolefor miR-20a, since overexpression of this miRNA decreased apoptosis in a prostate cancercell line, while inhibition of miR-20a by an antisense oligonucleotide resulted in increasedcell death after doxorubicin treatment. This anti-apoptotic role of miR-20a may explain someof the oncogenic capacities of the mir-17-92cluster.The Present study emphasis on the expression of miR-20a in human glioma tissues andits effect on the proliferation of human glioma cells.Methods The expression of miR-20a was detected in human normal brain tissues andglioma tissues by Real-time reverse transcriptase-polymerase chain reaction (RT-PCR).miR-20a mimics were synthesized and transfected into U251cells via liposome. Theproliferation of the transfected U251cells were detected using MTT assay and flowcytometry.Results (1) The glioma tissues showed significantly upregulated expression of miR-20acompare with normal brain tissues (P=0.035).(2) The expression level of miR-20a inhigh-grade gliomas was higher than that of low-grade.(3) miR-20a mimics significantlyenhanced the proliferation and number in S stage of U251cells.Conclusion miR-20a shows potent promote effect on the growth of glioma cells,suggesting increased expression of miR-20a may play a role in the pathogenesis of humanglioma.
Keywords/Search Tags:glioma, hsa-miR-20a, target gene
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