Biomedical Sciences ETDs

Grace Okello

Publication Date

7-1-2014

Abstract

RNA binding proteins (RBPs) and microRNAs (miRNAs) control gene expression post-transcriptionally by targeting mRNAs for translational activation, repression, or degradation. To date, aberrant expression of RBPs and miRNAs has been observed in many types of human cancers. We have shown the overexpression of Cold Inducible RNA binding protein (CIRP) in human breast cancer cell lines as compared to nontumorigenic and nontransformed breast epithelial cells. Others have shown cytoplasmic CIRP to be upregulated in a subset of breast tumors. Little is known about CIRP targets or its role in breast cancer. RBP Human antigen R (HuR), whose cytoplasmic localization is associated with aggressive breast cancer, and miR-125a, which is decreased in breast cancer, also have a poorly understood contribution to the etiology of breast cancer. Our studies in breast cancer cell lines have shown that CIRP overexpression upregulates HuR and proliferation, whereas miR-125a expression downregulates HuR and suppresses proliferation. In this study, we address whether this post-transcriptional regulatory network is disrupted in clinical samples of human breast tumors by assessing the nuclear to cytoplasmic distribution of HuR, CIRP and miR-125a in three primary breast tumor subtypes: ER+PR+HER2-, ER+HER2- and ER-PR-HER2-, and matched normal breast tissue. Results show that the nuclear to cytoplasmic ratio of CIRP was increased in ER+PR+HER2- tumors compared to normal matched tissues, while HuR and miR-125a nuclear to cytoplasmic ratios show no significant difference between the tumors and matched normal tissues. The nuclear to cytoplasmic ratio of HuR is increased in the ER-PR-HER2- tumors compared to the other tumor subtypes, and this ratio correlates positively with proliferation. HuR and CIRP nuclear to cytoplasmic ratios positively correlate in ER+PR+HER2- tumors as do HuR and miR-125a nuclear to cytoplasmic ratios. Lastly, the nuclear to cytoplasmic ratio of miR-125a is decreased in ER-HER2+ tumors compared to ER+PR+HER2- tumor subtype. This brings us to the conclusion that the post transcriptional regulatory network is relevant to ER+PR+HER2- tumors and the ER-PR-HER2- tumors.

Keywords

Cold inducible RNA Binding Protein

Document Type

Thesis

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Masters

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Cook, Linda

Second Committee Member

Trujillo, Kristina

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