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The Function Of MicroRNA-4728-5p In Breast Tumourgenesis

Posted on:2016-10-14Degree:MasterType:Thesis
Country:ChinaCandidate:X L WangFull Text:PDF
GTID:2284330461956325Subject:Pharmaceutical engineering
Abstract/Summary:PDF Full Text Request
MicroRNAs (miRNAs) are a class of endogenously expressed, small non-coding RNAs with the length of 19-25nt. Through base-pairing with 3’-untranslated region (3-UTR) of messenger RNA (mRNA), miRNAs depress expression of target genes at the post-transcriptional level by inhibiting translation of mRNA or by destabilizing mRNA. Under the normal circumstance, miRNAs are involved in a variety of basic biological processes, such as development, proliferation, differention,apotosis and stress responses. In recent years, deregulated expression of miRNAs has been reported to be assaciated with many diseases.This article starts at Erbb2 in the process of breast cancer, founding that high Erbb2 expression in the process of breast cancer, and Erbb2 expresss its intron miR-4728-5p, we found the Erbb2 and miR-4728-5p had a significant rise in the breast cancer tissues using real-time fluorescent quantitative PCR.Bioinformatics prediction shows that EBP1 (ErbB3 binding protein 1) is the target genes of miR-4728-5p, and EBP1 in specific inhibits Erbb2 mRNA and protein level.Accordingly, EBP1 protein expression in breast cancer brings down.So we put forward a hypothesis, in the process of breast cancer, Erbb2 expression rise, resulting in miR-4728-5p expression rises, and miR-4728-5p inhibits EBP1 level to promote Erbb2 expression to rise further, to form a positive cycle.Luciferase reporter gene experiments show that miR-4728-5p and EBP1 mRNA 3’UTR combination.In breast cancer cell lines,we express or inhibit miR-4728-5p, can reduce or increase EBP1 protein levels, corresponding results in the decrease or increase of Erbb2 protein levels,ultimately affect the breast cancer cell proliferation and migration ability.The EBP1 over expression plasmid lack 3’UTR, therefore its expression from the miRNA regulation, can reply miR-4728-5p for EBPl inhibition, lift the miR-4728-5 p’s influence on the signal path and its influence on breast cancer cell proliferation and migration ability. And the promotion of migration of BT474 cells by miR-4728-5p could be reversed by overexpressing EBP1 ORF (open reading frame) vector,which was not regulated by miRNA for lacking 3’-UTR.In summary, deregulation of miRNAs was found to be highly associated with cancer progression. miR-4728-5p was upregulated in breast cancer respectively, and functioned as oncogenes by regulating proliferation or migration of tumour cells. These studies expanded the role of miRNAs in tumourgenesis, and provided new targets for the researches and therapies of cancer.
Keywords/Search Tags:miR-4728-5p, EBP1, Erbb2, breast cancer, cell proliferation, cell migration
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