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The regulation of plexin B1 expression in prostate cancer metastasis

Damola, AB; (2016) The regulation of plexin B1 expression in prostate cancer metastasis. Doctoral thesis , UCL (University College London). Green open access

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Abstract

Prostate cancer is a significant disease affecting most men as they age. Although the overall lifetime mortality from the disease is about 3% the disease has a high prevalence and the treatment for the disease carries with it unwanted morbidity. Our group has shown that plexin B1 protein expression is elevated in prostate cancer and have suggested a link with metastatic prostate cancer. The mechanism for the increased expression of plexin B1 in prostate cancer is unknown, the aim of this study was to elucidate the cause for this upregulation. I hypothesized that microRNAs are linked with the increased expression of plexin B1, either through loss of miRNA binding sites in the 3’UTR of plexinB1 mRNA or through loss of specific miRNAs that regulate plexinB1 expression. I found no evidence for plexinB1 mRNA variants with truncated 3’UTR resistant to miRNA down regulation. Two splice variants were identified in prostate cancer cells that are predicted to alter plexinB1 function, one being variant R hitherto unproven in literature. I performed an insilico and an in vitro functional screen to identify candidate miRNAs that regulate plexinB1 expression. The candidate miRNAs were then assessed to establish if they directly bound to the 3’UTR of plexinB1 and regulated expression of a reporter gene and to determine if they had any effect on endogenous plexinB1 mRNA and protein levels in prostate cancer cell lines. MiRNAs 199a and miRNA 214-3p reduced expression of the reporter gene and endogenous plexinB1, suggesting that these miRNAs negatively regulate plexinB1 expression directly by binding to the 3’UTR of plexinB1. MiRNA 1 was found to down regulate endogenous plexinB1 expression probably indirectly. I conclude that there is a role for specific microRNAs in regulating plexin B1 expression with potential for prostate cancer therapy but further studies are needed to validate my findings.

Type: Thesis (Doctoral)
Title: The regulation of plexin B1 expression in prostate cancer metastasis
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
URI: http://discovery.ucl.ac.uk/id/eprint/1485818
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