Human Antigen R (HuR) is a RNA binding protein and a master-regulator of other RNA binding proteins. HuR controls the post-transcriptional fate of thousands of mRNA transcripts and also controls the survival and proliferation of cancer cells. HuR mis-regulates the fates of various mRNAs which transforms normal cells into cancer cells and ensures their survival. MicroRNA antagonists protect mRNAs from microRNA decay. Near the same position HuR mRNA is targeted for decay by miR-9, miR-125a, and miR-133ab. A ssDNA microRNA antagonist protects HuR mRNA from microRNA decay which changes HuR protein expression. The ssDNA microRNA antagonist induced changes in HuR protein expression and decreased phosphorylation of AKTSER473 in Prostate, Breast, and Ovarian cancer cells. AKT is a powerful regulator of cell metabolism. HuR is a powerful regulator of cancer. The ssDNA controls both. Chapter One describes HuR control of mRNA decay processes and HuR related cancer cells traits. Chapter Two describes a 22-NT sequence in HuR mRNA which led to design of a ssDNA oglionucleotide protector of protect HuR mRNA. Chapter 3 describes in-vitro tests in PC3, Du145, MatLyLu Prostate Cancer, MCF-7 Breast and SV-OV-3 Ovarian Cancers and in-vivo tests in Dunning R3327 Rat Prostate Cancer model. Chapter 4 discusses the results of deregulating HuR expression and the discovery that deregulating HuR inhibits the AKT pathway.
|Commitee:||Chen, Xi, Jackson, William|
|School:||University of California, Davis|
|School Location:||United States -- California|
|Source:||DAI-B 75/10(E), Dissertation Abstracts International|
|Subjects:||Biology, Medicine, Pharmacy sciences|
|Keywords:||Akt, Cancer, Human antigen r, Hur, Inhibitor, Prostate|
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