The functional characterisation of potential oncogenic roles of the human germ line genes PRDM9 and TEX19

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Documents

  • Fahad Alharthi

    Research areas

  • PhD, School of Natural Sciences, cancer/testes antigen genes, genetics, PRDM9, TEZ19, epigenetics, molecular biology

Abstract

Cancer cells acquire a number of abnormal epigenetic and / or genetic properties. These enable cancer cells to grow, spread and escape the action of therapeutic and immunologic targeting. An important feature of many cancers is the re-activation of a set of genes which are normally expressed during distinct development stages. These genes include the germline genes. Cancer Testis Antigen (CTA) genes are normally expressed in male germ cells in the adult testes and variety of cancer cells. Understanding this group of genes has great significance in cancer biology. This research is aimed at investigation of the functions of two germ specific CTA genes, namely PRDM9 and TEX19, both of which are activated in several kinds of tumours.

PRDM9 has histone methyltransferase activity to coordinate meiotic recombination hotspot activation. Activity the murine orthologue of human PRDM9, Meisetz, has been described as a meiotic recombination activator which is also involved in regulation of transcription for other meiosis specific genes. This current research indicates that PRDM9 can affect cancer cell proliferation and may transcriptionally regulate other germline genes in cancer cells.

TEX19 functions in the germ line to mediate an array of process. TEX19 has recently been demonstrated to be an oncogenic driver with potential role in self-renewal and proliferation of cancer cells. This current research confirmed that TEX19 depletion affects proliferation of cancer cells. Also, it was found that siRNA depletion of TEX19 caused considerable decrease in histone H3K9Ac, showing a potential contribution of TEX19 to epigenetic regulation of chromatin and / or chromosomal dynamics. Finally, we found that TEX19 might control L1-ORF1p, which is a protein encoded by LINE-1 that is needed for retro-transposition. This feature shows both commonalties and distinctions to the reported activities of murine Tex19.1. This might reflect fundamental species differences, or specific TEX19 functions in cancer cells. We put forward a model in which we propose TEX19 functions in oncogenesis as a nucleic acid mimetic.

Details

Original languageEnglish
Awarding Institution
  • Bangor University
Supervisors/Advisors
Award date3 Aug 2020