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LncRNA PVT1 Associates with c-Myc and Stabilizes Oncogenic Signaling in Prostate Cancer
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PublisherThe University of Arizona.
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AbstractUnderstanding the factors that affect c-Myc in prostate cancer is critical to developing an effective means of treatment for aggressive, castration-resistant forms of the disease. Myc is an oncogene known to be overexpressed and stabilized in many types of cancer, prostate included. Recent insights into breast cancer have revealed that Myc protein retains a longer half-life in cancer cells, but the cause for this has yet to be deduced. Due to its close proximity and proven interaction with Myc, I propose that the lncRNA PVT1 is stabilizing Myc and facilitating its activation of target genes in castration-resistant prostate cancer. To explore this hypothesis, metastatic prostate cancer DU145 cells were transfected with both siRNAs and ASOs targeting PVT1. Cells were analyzed for changes in different protein levels, as well as binding partners, through the use of immunoprecipitation and western blot. These results were verified with RT-qPCR data to confirm knockdown levels of PVT1. Proliferation assays were also conducted to explore the proliferative abilities of cells when PVT1 levels were decreased. Transfection of PVT1 with siRNA yielded about a 50% knockdown, while ASO targeting brought PVT1 levels down 80%. PVT1 inhibition had different effects on the level of c-Myc in cells depending on the method of transfection used--while transfection with anti-PVT1 siRNAs slightly decrease the amount of c-Myc protein in the cell, transfection using ASOs significantly increases c-Myc. Most importantly, proliferation of DU145 cells decreased with PVT1 knockdown by ASOs. Removal of this lncRNA, therefore, hinders that oncogenic potential for growth of prostate cancer cells. Since Myc poses a difficult target for cancer therapy, any new method to mitigate its oncogenic signaling would be invaluable. Targeting lncRNA PVT1 may be a successful method of doing just that, but more work needs to be done to explore the effects of different knockdown strategies. It is clear, however, that the relationship between Myc and PVT1 is a convoluted interaction that warrants further research. A breakthrough in this area could lead to huge improvements in the way prostate cancer is diagnosed and treated.
Degree ProgramGraduate College
Cellular and Molecular Medicine