Type
Text
Type
Thesis
Advisor
Cao, Jian | Ju, Jingfang
Date
2015-05-01
Keywords
cell migration, CEMIP, microRNA-128, post-transcriptinal regulation | Biology
Department
Department of Biochemistry and Cell Biology.
Language
en_US
Source
This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.
Identifier
http://hdl.handle.net/11401/76902
Publisher
The Graduate School, Stony Brook University: Stony Brook, NY.
Format
application/pdf
Abstract
Cell 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. | 25 pages
Recommended Citation
Zhang, Qian, "miR-128 Inhibits Cell Migration via Downregulation of CEMIP" (2015). Stony Brook Theses and Dissertations Collection, 2006-2020 (closed to submissions). 2776.
https://commons.library.stonybrook.edu/stony-brook-theses-and-dissertations-collection/2776