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The medical biomarker and oncogenic potential of the human cancer- and stem/germ cell-specific gene TDRD12

Oyouni, Atif Abdulwahab A. (2016) The medical biomarker and oncogenic potential of the human cancer- and stem/germ cell-specific gene TDRD12. PhD thesis, Prifysgol Bangor University.

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Abstract

Cancer is a common illness that affects many people across the world each year. Cancer mortality is often due not only to the limitations of existing therapies but also to its late diagnosis. In this light, efficient and effective tools to target and diagnose cancer in its early stages will make an enormous significant impact on improving the survival of cancer patients. Cancer/germ-line or cancer/testis antigen (CTA) genes are expressed in a tumour-specific fashion so can provide a powerful source of cancer biomarker/therapeutic target. Additionally, these genes may have oncogenic activity. In this study, we identify a novel human cancer- and stem/germ cell-specific gene, TDRD12, which may serve as a biomarker, therapeutic target and may have oncogenic activity. The expression of TDRD12 is found in human pluripotent embryonal carcinoma cells, human induced pluripotent stem cells, embryonic stem cells and colon adenocarcinoma cells. This indicates that TDRD12 might have stem cell and cancer stem cell (CSC) specificity, so it might play a role in conferring stemness on cancer cells. TDRD12 might also be required for the germ-line/stem cell regulation of retro elements (REs) and endogenous retro viruses (HERVs). Therefore, we establish that TDRD12 controls the RE/HERV expression levels in human germ-line tumour cells. We demonstrate that human PIWIL2 protein becomes depleted upon siRNA reduction of TDRD12 in pluripotent embryonal carcinoma cells, suggesting a functional regulatory relationship. Human PIWIL1 and TDRD12-T17 antibodies have consistent co-localisation, and they appear to have similar sub-cellular localisation patterns; these two antibodies localise in the same cells in the testis, which suggests a cofunction of these proteins. TDRD12 was further validated and analysed to identify its medical molecular and biological functions, as well as its possible application in developing human cancer therapies. The protein encoded by this gene might also be promising targets for new cancer therapies and clinical uses.

Item Type: Thesis (PhD)
Subjects: Degree Thesis
Departments: College of Natural Sciences > School of Biological Sciences
Degree Thesis
Date Deposited: 14 Jul 2016 11:52
Last Modified: 14 Jul 2016 11:52
URI: http://e.bangor.ac.uk/id/eprint/6594
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