URM1 Promoted Tumor Growth and Suppressed Apoptosis via the JNK Signaling Pathway in Hepatocellular Carcinoma
URM1 Promoted Tumor Growth and Suppressed Apoptosis via the JNK Signaling Pathway in Hepatocellular Carcinoma
复制标题
URM1 通过 JNK 信号通路促进肝细胞癌肿瘤生长并抑制细胞凋亡
DOI：
10.2147/ott.s258843
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发表时间：
2020-01-01
影响因子：
4
通讯作者：
Chen, Zhong
中科院分区：
文献类型：
--
作者：
Cheng, Xin;Zhang, Yu;Chen, Zhong
目的 泛素相关调节因子 1 (URM1) 是泛素样调节因子家族的成员，在氧化应急反应机制中充当翻译后蛋白调节因子。前期研究表明URM1可能参与细胞凋亡过程，并可能在JNK信号通路中发挥作用。在本研究中，我们旨在探讨URM1在HCC进展中的作用和可能的机制。患者和方法通过免疫组织化学测定90对匹配的肝癌和邻近非癌组织中URM1的表达。分别通过CCK-8、集落形成、TUNEL染色、伤口愈合实验和Transwell验证URM1对HCC细胞增殖、凋亡、迁移和侵袭能力的影响。然后，通过裸鼠肝癌异种移植模型探讨URM1对体外皮下肿瘤形成的影响。最后，通过蛋白质印迹分析URM1敲低样本中凋亡相关蛋白的表达。结果本研究中，与配对的癌旁非癌组织相比，肝癌组织中URM1的表达较高（P <0.01）。 Kaplan-Meier 生存分析显示，URM1 高表达与预后不良显着相关（P <0.05）。此外，URM1敲低可抑制肝癌细胞的增殖和迁移。此外，URM1敲低促进肝癌细胞凋亡。同时，URM1敲低抑制肝癌裸鼠异种移植模型中的肿瘤生长。此外，URM1敲低下调了凋亡相关因子JNK1/2和TP53的表达，并上调了JNK1/2和P53的磷酸化。结论 综上所述，我们的结果表明肝癌组织中URM1表达增加，URM1敲低抑制肝癌细胞的增殖和迁移并加速细胞凋亡。 URM1 高表达与 HCC 患者预后不良相关。
Objective Ubiquitin-related modifier 1 (URM1) is a member of the ubiquitin-like regulator family, which acts as a post-translational protein modifier in the oxidative emergency response mechanism. Previous studies have shown that URM1 may be involved in the process of apoptosis and may play a role in JNK signaling pathway. In this study, we aimed to investigate the role and possible mechanism of URM1 in HCC progression. Patients and Methods Expression of URM1 was determined in 90 pairs of matched liver cancer and adjacent non-cancerous tissues by immunohistochemistry. The impacts of URM1 on HCC cell proliferation, apoptosis, migration and invasion capacities were verified by CCK-8, colony formation, TUNEL staining, wound healing assay and transwell, respectively. Then, the effect of URM1 on subcutaneous tumor formation in vitro was explored by nude mouse xenograft model of liver cancer. Finally, the expression of apoptosis-related proteins was analyzed in URM1 knockdown samples by Western blotting. Results In this study, compared with paired adjacent non-cancerous tissues, the expression of URM1 was higher in liver cancer tissues (P <0.01). Kaplan–Meier survival analysis showed that high URM1 expression was significantly associated with poor prognosis (P <0.05). Moreover, URM1 knockdown inhibited liver cancer cell proliferation and migration. Furthermore, URM1 knockdown promoted apoptosis of liver cancer cells. At the same time, URM1 knockdown inhibited tumor growth in nude mouse xenograft model of liver cancer. In addition, URM1 knockdown downregulated the expression of the apoptosis-related factors JNK1/2 and TP53 and upregulated the phosphorylation of JNK1/2 and P53. Conclusion In summary, our results suggested that URM1 expression is increased in liver cancer tissues, and URM1 knockdown inhibits the proliferation and migration of liver cancer cells and accelerates apoptosis. High URM1 expression is associated with poor prognosis in patients with HCC.