Department of Hematology, the First Hospital of Lanzhou University, Lanzhou 730000, P.R. China
Department of Hematology, the First Hospital of Lanzhou University, Lanzhou 730000, P.R. China.
Biosci Rep. 2019 Apr 5;39(4). doi: 10.1042/BSR20190040. Print 2019 Apr 30.
Ubiquitin-specific peptidase 39 (USP39) is one member of the cysteine proteases of the USP family, which represents the largest group of DeUbiquitinases with more than 50 members in humans. The roles of USP39 in human cancer have been widely investigated. However, the roles of USP39 in human leukemia and the underlying mechanism remain unknown. Here we reported the function of USP39 in human leukemia. We observed that the expression of was up-regulated in human leukemia cells and the high expression of was correlated with poor survival of the patients with leukemia. Lentivirus-mediated knockdown of repressed the proliferation and colony formation of human leukemia cell lines HL-60 and Jurkat cells. Mechanism study showed that knockdown induced the arrest of cell cycle and apoptosis of leukemia cells. In addition, our microarray and bioinformatic analysis demonstrated that USP39 regulated diverse cellular signaling pathways that were involved in tumor biology, and several pivotal genes (, and ) have been validated by quantitative real-time polymerase chain reaction. Knockdown or partially restored the proliferation rate of leukemia cells with knockdown. Taken together, our findings implicate that USP39 promotes the development of human leukemia by regulating cell cycle, survival, and proliferation of the cells.
泛素特异性肽酶 39(USP39)是泛素特异性蛋白酶家族的胱氨酸蛋白酶之一,是具有超过 50 个成员的最大去泛素化酶家族之一。USP39 在人类癌症中的作用已被广泛研究。然而,USP39 在人类白血病中的作用及其潜在机制尚不清楚。在这里,我们报道了 USP39 在人类白血病中的功能。我们观察到,在人类白血病细胞中上调表达,并且高表达与白血病患者的不良生存相关。慢病毒介导的 USP39 敲低抑制了人类白血病细胞系 HL-60 和 Jurkat 细胞的增殖和集落形成。机制研究表明,USP39 敲低诱导白血病细胞周期停滞和细胞凋亡。此外,我们的微阵列和生物信息学分析表明,USP39 调节多种参与肿瘤生物学的细胞信号通路,并且已经通过定量实时聚合酶链反应验证了几个关键基因(、和)。USP39 敲低或部分恢复了 USP39 敲低的白血病细胞的增殖率。总之,我们的研究结果表明,USP39 通过调节细胞周期、细胞存活和增殖促进人类白血病的发展。