Research Paper Volume 12, Issue 23 pp 23647—23667
Identification of the novel Np17 oncogene in human leukemia
- 1 Department of Hematology, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China
- 2 Cancer Institute, Zhejiang University, Hangzhou 310009, China
- 3 College of Letters and Sciences, University of California-Berkeley, Berkeley, CA 94720, USA
- 4 Molecular Oncology Program and Department of Diabetes Complications and Metabolism, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- 5 Department of Hematology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310009, China
- 6 Department of Pathology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China
- 7 Zhejiang Academy of Medical Sciences, Hangzhou 310012, China
- 8 Institute of Hematology, Zhejiang University, Hangzhou 310009, China
Received: May 11, 2020 Accepted: July 9, 2020 Published: November 21, 2020
https://doi.org/10.18632/aging.103808How to Cite
Copyright: © 2020 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
We previously defined the HERV-K Np9 as a viral oncogene. Here we report the discovery of a novel oncogene, Np17, which is homologous to the viral Np9 gene and predominantly present in Hominoidea. Np17 is located on chromosome 8, consists of 7 exons, and encodes a 16.8kDa nuclear protein with149 amino-acid residue. Functionally, knockdown of Np17 induced growth inhibition of leukemia cells, whereas enforced expression of Np17 promoted growth of leukemia cells in vitro and in vivo. In human leukemia, Np17 was detected in 59.65% (34/57) of acute myeloid leukemia (AML) patients examined and associated with refractory/relapsed AML. Mechanistically, Np17 decreased p53 levels and its mechanism might be involved in recruiting nuclear MDM2 to p53 for ubiquitin-mediated degradation. These findings reveal that Np17 is a novel oncogene associated with refractory/relapsed leukemia.