NANOGP8 is a human (Homo sapiens) retrogene, expressed predominantly in cancer cells where its protein product is tumorigenic. It arose through retrotransposition from its parent gene, NANOG, which is expressed predominantly in embryonic stem cells. Based on identification of fixed and polymorphic variants in a genetically diverse set of human NANOG and NANOGP8 sequences, we estimated the evolutionary origin of NANOGP8 at approximately 0.9 to 2.5 million years ago, more recent than previously estimated. We also discovered that NANOGP8 arose from a derived variant allele of NANOG containing a 22-nucleotide pair deletion in the 3' UTR, which has remained polymorphic in modern humans. Evidence from our experiments indicates that NANOGP8 is fixed in modern humans even though its parent allele is polymorphic. The presence of NANOGP8-specific sequences in Neanderthal reads provided definitive evidence that NANOGP8 is also present in the Neanderthal genome. Some variants between the reference sequences of NANOG and NANOGP8 utilized in cancer research to distinguish RT-PCR products are polymorphic within NANOG or NANOGP8 and thus are not universally reliable as distinguishing features. NANOGP8 was inserted in reverse orientation into the LTR region of an SVA retroelement that arose in a human-chimpanzee-gorilla common ancestor after divergence of the orangutan ancestral lineage. Transcription factor binding sites within and beyond this LTR may promote expression of NANOGP8 in cancer cells, although current evidence is inferential. The fact that NANOGP8 is a human-specific retro-oncogene may partially explain the higher genetic predisposition for cancer in humans compared with other primates.
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http://dx.doi.org/10.1534/g3.112.004366 | DOI Listing |
Cureus
September 2024
Neurosurgery, Emergency Clinical County Hospital Of Targu Mures, Targu Mures, ROU.
Glioblastoma (GB) is the most common brain malignancy occurring in adult patients having an extremely low overall survival. Therefore, it is paramount to establish reliable and accurate diagnostic and prognostic markers to guide a personalized and more effective treatment. Molecular characterization of the tumor is the ultimate goal in GB management and comprises, among others, the study of the extracellular vesicles (EVs).
View Article and Find Full Text PDFInt J Mol Sci
July 2024
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA.
Extracellular vesicles (EVs) are garnering attention as a safe and efficient biomolecule delivery system. EVs intrinsically play a crucial role in intercellular communication and pathophysiology by transporting functionally active DNA molecules. The internalized DNA pleiotropically affects the recipient cells.
View Article and Find Full Text PDFHeliyon
May 2024
Department of Gastroenterology, Lanzhou University Second Hospital, Lanzhou, PR China.
Background: Colon cancer (CC) stem cells can self-renew as well as expand, thereby promoting tumor progression and conferring resistance to chemotherapeutic agents. The acetyltransferase NAT10 mediates N4-acetylcytidine (acC) modification, which in turn drives tumorigenesis, metastasis, stemness properties maintenance, and cell fate decisions. Nonetheless, the specific involvement of acC modification mediated by NAT10 in regulating stemness and chemosensitivity in CC remains undetermined.
View Article and Find Full Text PDFPLoS One
January 2023
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, United States of America.
Exosomes participate in intercellular communication by transporting functionally active molecules. Such cargo from the original cells comprising proteins, micro-RNA, mRNA, single-stranded (ssDNA) and double-stranded DNA (dsDNA) molecules pleiotropically transforms the target cells. Although cancer cells secrete exosomes carrying a significant level of DNA capable of modulating oncogene expression in a recipient cell, the regulatory mechanism is unknown.
View Article and Find Full Text PDFCells
November 2022
Basic Medical Sciences Department, College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar.
Somatic cells are reprogrammed with reprogramming factors to generate induced pluripotent stem cells (iPSCs), offering a promising future for disease modeling and treatment by overcoming the limitations of embryonic stem cells. However, this process remains inefficient since only a small percentage of transfected cells can undergo full reprogramming. Introducing miRNAs, such as miR-294 and miR302/3667, with reprogramming factors, has shown to increase iPSC colony formation.
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