Cai Jing, Liu Tiande, Huang Peng, Yan Wei, Guo Changkuo, Xiong Le, Liu Anwen
Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
Biochem Biophys Res Commun. 2017 Apr 22;486(1):184-190. doi: 10.1016/j.bbrc.2017.03.025. Epub 2017 Mar 9.
Ubiquitin specific protease 39 (USP39) is one of the deubiquitinating enzymes without ubiquitin protease activity, which has been implicated in the progression of several cancers. However, the role of USP39 in pancreatic cancer (PC) is largely unknown. In present study, we found that USP39 expression was elevated in PC tissues than adjacent non-tumor tissues. Importantly, we demonstrated that overexpression of USP39 is closely correlated with tumor progression and poor survival in PC patients. Furthermore, high USP39 expression was observed in PC cell lines and ectopic expression of USP39 significantly enhanced in vitro cell proliferation and promoted in vivo tumor growth, whereas silencing USP39 suppressed growth of PC cells. Besides, our experimental data revealed that knockdown of USP39 induced cell apoptosis through inhibition of AKT signaling pathway in PC cells. Moreover, USP39 was a direct target of miR-133a, a microRNA that has been reported to be involved in progression of PC. Taken together, our data provide a novel PC regulatory axis that is miR-133a/USP39, the dysfunction of which drives diverse aspects of the progression of PC.
泛素特异性蛋白酶39（USP39）是一种不具有泛素蛋白酶活性的去泛素化酶，它与多种癌症的进展有关。然而，USP39在胰腺癌（PC）中的作用在很大程度上尚不清楚。在本研究中，我们发现PC组织中USP39的表达高于相邻的非肿瘤组织。重要的是，我们证明USP39的过表达与PC患者的肿瘤进展和不良生存密切相关。此外，在PC细胞系中观察到USP39高表达，USP39的异位表达显著增强了体外细胞增殖并促进了体内肿瘤生长，而沉默USP39则抑制了PC细胞的生长。此外，我们的实验数据表明，敲低USP39通过抑制PC细胞中的AKT信号通路诱导细胞凋亡。此外，USP39是miR-133a的直接靶点，miR-133a是一种据报道参与PC进展的微小RNA。综上所述，我们的数据提供了一个新的PC调控轴，即miR-133a/USP39，其功能障碍驱动了PC进展的多个方面。
