MicroRNAs in Breast and Endometrium

来源 :BIT‘s2nd Annual World Cancer Congess-2009 (2009第二届癌症大会) | 被引量 : 0次 | 上传用户:wj781228
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  MicroRNAs are endogenous RNA molecules (~22 nt) that are involved in the posttranscriptional regulation of target genes.Reports suggest that microRNA profiles differ in normal versus tumor tissues, can be used to classify tumor types and correlate with the clinical prognosis.Individual miRNAs have been shown to regulate the expression of critical genes involved in proliferation, apoptosis, and malignant transformation.In this study, we will describe the characterization of specific target genes and the microRNA profiling studies we have done on endometrial carcinomas.In particular, the microRNA mediated regulation of the protein Annexin A1 (ANXA1), a mediator of apoptosis and inhibitor of cell proliferation in various types of cancers.We investigated whether decreasedANXA1 expression was mediated by microRNA.Using computational analysis, we identified miR-584, miR-196a and miR-196b as potential microRNAs targeting ANXA1.Only miRNA-196a showed significant inverse correlation with ANXA 1 mRNA levels in 12 cancer cell lines of breast, endometrial and esophageal origin (Pearsons correlation-0.66, p=0.019) identifying this as the candidate miRNA targeting ANXA 1.Increasing miR-196a levels in ceils by miR-196a mimics resulted in decreased ANXA1 mRNA and protein.Additionally, miR-196a mimics inhibited luciferase expression in luciferase plasmid reporter that included predicted miR-196a recognition sequence from ANXA1 3-untranslated region confirming miR-196a directly targets ANXA1.This study demonstrates a novel microRNA-mediated mechanism of regulation of ANXA1 expression in cancer.
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