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dc.identifier.urihttp://hdl.handle.net/11401/76902
dc.description.sponsorshipThis work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.en_US
dc.formatMonograph
dc.format.mediumElectronic Resourceen_US
dc.language.isoen_US
dc.publisherThe Graduate School, Stony Brook University: Stony Brook, NY.
dc.typeThesis
dcterms.abstractCell Migration Inducing Protein (CEMIP) has been demonstrated to promote cancer progression by enhancing cancer cell migration, hence increasing cancer invasion and metastasis. Upregulated expression of CEMIP in human cancers is associated with poor patient survival rate. Experimental data demonstrated that CEMIP is exclusively detected in human colon cancer cells examined by immunohistochemistry staining. Interestingly, enhanced expression of CEMIP was found in cancer cells located at the invasive front. However, the regulatory mechanism of enhanced CEMIP expression in cancer has not been fully characterized. The aim of this study is to unravel the regulatory mechanism of CEMIP in cancer progression by focusing on post-transcriptional regulation of CEMIP in cancer cells. Employing a bioinformatics tool for identification of potential targeting sites by microRNA (miRNA) within the CEMIP 3'-untranslatioed region (3'UTR), miRNA -128(1,2) responding elements within the 3'UTR was identified. By surveying human cancer cell lines for CEMIP expression, downregulation of CEMIP was found in aggressive human cancer cell lines and inversely correlated with endogenous CEMIP expression. This observation is in agreement with miR128-1 and CEMIP expression in human colon cancer specimens examined by qPCR. To further determine the correlation of miRNA-128-1 with CMEIP expression, a miR128 inhibitor, called sponge, was generated. When the miR128 sponge was expressed in less aggressive cancer cell lines, CEMIP expression was rescued suggesting specific role of miR128-1 in CEMIP expression. miR128-1 no longer affects CEMIP gene expression once the miR128 binding site within the 3' UTR of CEMIP was mutated. Functionally, overexpression of miR-128-1 in the aggressive cancer cells reduces cell migration These findings suggest a novel regulatory pathway in invasive cancer cells, in which the upregulated transcription factor, Snail, reduces the expression of miR128-1, leading to stabilizing CEMIP mRNA, so expressed CEMIP then induce cancer cell migration.
dcterms.available2017-09-20T16:51:24Z
dcterms.contributorCao, Jianen_US
dcterms.contributorJu, Jingfangen_US
dcterms.creatorZhang, Qian
dcterms.dateAccepted2017-09-20T16:51:24Z
dcterms.dateSubmitted2017-09-20T16:51:24Z
dcterms.descriptionDepartment of Biochemistry and Cell Biology.en_US
dcterms.extent25 pg.en_US
dcterms.formatMonograph
dcterms.formatApplication/PDFen_US
dcterms.identifierhttp://hdl.handle.net/11401/76902
dcterms.issued2015-05-01
dcterms.languageen_US
dcterms.provenanceMade available in DSpace on 2017-09-20T16:51:24Z (GMT). No. of bitstreams: 1 Zhang_grad.sunysb_0771M_12248.pdf: 7176945 bytes, checksum: f51f6a313bdcc8da38b5cb12205f3808 (MD5) Previous issue date: 2015en
dcterms.publisherThe Graduate School, Stony Brook University: Stony Brook, NY.
dcterms.subjectBiology
dcterms.subjectcell migration, CEMIP, microRNA-128, post-transcriptinal regulation
dcterms.titlemiR-128 Inhibits Cell Migration via Downregulation of CEMIP
dcterms.typeThesis


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