NSD家族组蛋白甲基化转移酶与肿瘤发生

The NSD Family of Histone Methyltransferase and Tumorigenesis

组蛋白的修饰通过调节染色质结构的疏密程度从而影响基因转录等与DNA有关的生物学功能。NSD蛋白家族(nuclear receptor binding SET domain proteins)(包括NSD1-3)是一组与肿瘤发生相关的组蛋白甲基化转移酶,其中又以NSD2与肿瘤的关系最为密切。近年来的研究发现,NSD2在多发性骨髓瘤、神经母细胞瘤及肝癌等多种肿瘤中高表达,并且相关病人的预后较差。NSD2呈现多种原癌基因的特征:NSD2高表达促进细胞增殖、克隆形成、侵袭能力增强以及肿瘤移植物的生长等。然而,NSD1与NSD3虽然可以与核孔蛋白98 k Da(nucleoporin 98 k Da,NUP98)形成融合蛋白,在部分急性髓性白血病中有致瘤作用,但是它们本身却具有抑癌基因的特点。该文就NSD蛋白家族的最新研究进展作一综述,阐述了NSD蛋白家族在肿瘤发生发展中的作用及潜在的应用前景。

Histone modification regulates gene transcription and other DNA related biological functions through adjusting the structure of the chromatins. The NSD proteins （nuclear receptor binding SET domain proteins）, including NSD1-3, are a family of cancer related histone lysine methyltransferases, among which NSD2 is most closely associated with cancer. Recent studies showed that NSD2 was overexpressed in many cancers including multiple myeloma, neuroblastoma, hepatocyte carcinoma, etc. High expression of NSD2 was associated with poor prognosis of many cancer types. NSD2 has properties ofproto-oncogenes, as its overexpression promotes cell proliferation, colony formation, invasion and exograft growth. However, although NSD1 and NSD3 form fusion proteins with nucleoporin 98 kDa （NUP98） in AML and promote tumorgenesis, NSD1 and NSD3 alone behave more like tumor suppressors. Here, we reviewed the current knowledge on NSD family in tumorigenesis and prospect their special value in cancer management.