Identification of the novel Np17 oncogene in human leukemia

Bowen Wu; Yichao Gan; Ying Xu; Zhaoxing Wu; Ganyu Xu; Ping Wang; Chen Wang; Zhipeng Meng; Mengyuan Li; Jiawei Zhang; Haifeng Zhuang; Xuzhao Zhang; Linlin Yang; Jinfan Li; Xiaoxian Gan; Xiaofang Yu; Wendong Huang; Ying Gu; Rongzhen Xu

doi:10.18632/aging.103808

Identification of the novel Np17 oncogene in human leukemia

Aging (Albany NY). 2020 Nov 21;12(23):23647-23667. doi: 10.18632/aging.103808. Epub 2020 Nov 21.

Authors

Bowen Wu^{1

2}, Yichao Gan², Ying Xu^{1

2}, Zhaoxing Wu^{1

2}, Ganyu Xu³, Ping Wang^{1

2}, Chen Wang², Zhipeng Meng⁴, Mengyuan Li^{1

2}, Jiawei Zhang⁴, Haifeng Zhuang⁵, Xuzhao Zhang¹, Linlin Yang^{1

2}, Jinfan Li⁶, Xiaoxian Gan⁷, Xiaofang Yu², Wendong Huang⁴, Ying Gu^{1

2}, Rongzhen Xu^{1

2

8}

Affiliations

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.

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.

Keywords: Np17; Np9; P53; leukemia; oncogene.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Case-Control Studies
Cell Proliferation
Female
Gene Expression Regulation, Leukemic
HL-60 Cells
Humans
K562 Cells
Leukemia / genetics
Leukemia / metabolism*
Leukemia / pathology
Mice, Inbred NOD
Mice, SCID
Neoplasm Proteins / genetics
Neoplasm Proteins / metabolism*
Oncogene Proteins / genetics
Oncogene Proteins / metabolism*
Proteolysis
Proto-Oncogene Proteins c-mdm2 / metabolism
Signal Transduction
THP-1 Cells
Tumor Suppressor Protein p53 / metabolism
Ubiquitination

Substances

NP17 protein, human
Neoplasm Proteins
Oncogene Proteins
TP53 protein, human
Tumor Suppressor Protein p53
MDM2 protein, human
Proto-Oncogene Proteins c-mdm2