Identification of the novel Np17 oncogene in human leukemia.

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

doi:10.18632/aging.103808

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.

Highlights

Human endogenous retroviruses (HERVs) have resided in the human genome for several million years and makes up 8% of the human genome [1,2,3,4]
Given that we previously defined the viral np9 gene, which is aberrantly activated in human leukemia, as a potent oncogene [1], we attempted to search for cellular homologs of the viral oncogene np9 in NCBI database by performing alignment using Np9 protein sequence
We identified a cellular homolog of the viral np9 gene from Homo sapiens cDNA FLJ26472 fis containing an intact open reading frame (ORF) (450bp) (Supplementary Figure 1)

Summary

Introduction

Human endogenous retroviruses (HERVs) have resided in the human genome for several million years and makes up 8% of the human genome [1,2,3,4]. The majority of HERVs are dysfunctional due to multiple nonsense mutations, some are still active and may have potential functions [5,6,7,8,9,10,11], especially the HERV type K (HERV-K) family [12,13,14,15,16,17,18,19,20,21], which is the most recent entrant into the human genome, having entered 200,000 to 5 million years ago [22], and has been linked to oncogenesis [23]. Our previous studies revealed that the viral Np9 protein is an oncoprotein and potently activates a variety of pathways such as β-catenin, ERK, Akt and Notch, and promotes the growth of human leukemia stem/progenitor cells [1]. We have identified and characterized a novel cellular homolog of HERV-K np gene, which encodes a nuclear oncoprotein of 17kDa associated with human leukemia and is referred to as np gene

Methods

Results

Conclusion