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鉴定人白血病中的新型 Np17 癌基因。

Identification of the novel Np17 oncogene in human leukemia.

机构信息

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.

Cancer Institute, Zhejiang University, Hangzhou 310009, China.

出版信息

Aging (Albany NY). 2020 Nov 21;12(23):23647-23667. 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.

摘要

我们之前将 HERV-K Np9 定义为一种病毒癌基因。在这里,我们报告了一种新的癌基因 Np17 的发现,它与病毒 Np9 基因同源,主要存在于灵长类动物中。Np17 位于 8 号染色体上,由 7 个外显子组成,编码一个 16.8kDa 的核蛋白,含有 149 个氨基酸残基。功能上,Np17 的敲低诱导白血病细胞生长抑制,而 Np17 的强制表达促进白血病细胞在体外和体内的生长。在人类白血病中,在检查的 57 例急性髓细胞白血病(AML)患者中有 59.65%(34/57)检测到 Np17,与难治/复发的 AML 相关。在机制上,Np17 降低了 p53 水平,其机制可能涉及招募核 MDM2 到 p53 进行泛素介导的降解。这些发现表明 Np17 是一种与难治/复发白血病相关的新型癌基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f351/7762455/aa7bd4cda5fb/aging-12-103808-g001.jpg

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