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SETD2基因是调控哺乳动物表观遗传的一个重要基因,其编码的SETD2蛋白主要参与组蛋白甲基化修饰,与RNA聚合酶II作用介导转录延长及错配修复。小鼠SETD2结构异常通过下调H3K36me3而引起血管构建功能缺陷。在许多人类肿瘤(乳腺癌、肾癌及膀胱肿瘤等)中都发现了SETD2基因改变。近年来的研究表明,SETD2基因表达下调可促进白血病干细胞的自我更新,从而促进白血病的发生和发展。SETD2-H3K36me3信号通路可认为是肿瘤中常见的一种抑癌机制,这也为临床疾病诊断和治疗提供了新策略。但是,关于SETD2异常引起肿瘤的具体作用机制需要进一步研究。该文就SETD2基因的结构、功能及其在胚胎发育及成体肿瘤尤其是白血病中的作用机制作一综述。
The SETD2 gene is an important gene regulating mammalian epigenetics. The SETD2 protein is mainly involved in the histone methylation modification and mediates the elongation and mismatch repair with RNA polymerase II. Structural abnormalities in mouse SETD2 cause defects in vascular construction by down-regulating H3K36me3. SETD2 gene mutations have been found in many human tumors (breast, kidney and bladder tumors, etc.). In recent years, studies have shown that SETD2 gene expression can promote leukemia stem cell self-renewal, thereby promoting the occurrence and development of leukemia. SETD2-H3K36me3 signaling pathway can be considered as a common tumor suppressor mechanism, which also provides a new strategy for the diagnosis and treatment of clinical diseases. However, the specific mechanism of SETD2-induced tumorigenesis needs further study. This review summarizes the structure and function of the SETD2 gene and its mechanism of action in embryonic development and adult tumors, especially leukemia.