title: Does expression of the retrogene UTP14c in the ovary pre-dispose women to ovarian cancer?
abstract: It has been previously shown that the spermatogenesis associated retrogene, UTP14c, is expressed in over 50% of normal human ovaries and 80% of ovarian cancers. UTP14c is located on chromosome 13 as an intronless copy of the X-linked housekeeping gene, UTP14a. Like all spermatogenesis associated retrogenes, UTP14c is expressed in the testis and is essential for sperm production. It has no known role in the female and is not normally expressed in any cells or organs outside of the gonads. By comparison the protein encoded by UTP14a is found in all cell types and has a dual function. It is primarily involved in the biosynthesis of 18S ribosomal RNA in the nucleolus where it is a component of the U3 small nucleolar RNA associated protein complex. In addition, it down regulates TP53 in both the nucleus and cytoplasm by targeting it for proteolytic degradation. By analogy, we propose that the UTP14c peptide also targets TP53 for degradation. This in turn may prevent cells expressing UTP14c from entering apoptosis. The loss of TP53 in ovarian cells can also result in the down regulation of microRNA-145 (miR-145) expression. The loss of miR-145 can result in the activation of factors that promote oncogenesis and cellular pluripotency which in turn could lead to the development of ovarian cancer. We hypothesize that women, whose ovaries express UTP14c, are predisposed to ovarian cancer due to the disruption of protective signals that normally trigger TP53-mediated apoptosis and the dysregulation of genes that promote oncogenesis, such as c-Myc, that occurs when miR-145 synthesis is disrupted.
authors.affiliation: Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. jrohozin@wfubmc.edu
authors.forename: Jan
authors.initials: J
authors.lastname: Rohozinski
authors.forename: Creighton L
authors.initials: CL
authors.lastname: Edwards
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Anderson
mesh_terms: D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D008954:Models, Biological; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D010053:Ovary / Q000378:metabolism*; D020718:Ribonucleoproteins, Small Nucleolar / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D020718:Ribonucleoproteins, Small Nucleolar; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C117377:ribonucleoprotein, U3 small nucleolar