Neural precursor cell expressed, developmentally downregulated 8 promotes tumor progression and predicts poor prognosis of patients with bladder cancer

Abstract

Neddylation has been researched in many different human carcinomas. However, the roles of neural precursor cell expressed, developmentally downregulated 8 (NEDD8) in bladder cancer are still unknown. Our study was the first study which systematically investigated the possible functions of NEDD8 in bladder cancer (BC) progression. We carried out immunohistochemistry to explore associations between the expression of NEDD8 in tumor tissues and clinical outcomes of patients. RT‐qPCR and western blot were used to detect the expressional levels of genes. The biological abilities of cell proliferation, migration and invasion were researched by in vitro and in vivo experiments. Results were as follows: Data from The Cancer Genome Atlas (TCGA) database showed that NEDD8 was overexpressed in BC tissues and was associated with poor patient survival. Results of immunohistochemistry found that NEDD8 was significantly associated with poor clinical outcomes of BC patients. Suppression of NEDD8 could inhibit the proliferation, migration and invasion of tumor cells. Knocking down NEDD8 could induce apoptosis and G2 phase arrest of cell cycle progression. In vivo, suppression of NEDD8 restricted growth and metastasis of tumors in mice. In conclusion, NEDD8 has important roles in regulating the progression of BC cells and was associated with poor prognosis of patients; hence, it may become a potential therapeutic target of BC.

NEDDylation negatively regulates ERRβ expression to promote breast cancer tumorigenesis and progression

“…We examined the components of the NEDDylation pathway in breast cancer tissue microarrays and different breast cancer cell lines and found that the components of NEDDylation cascade is overexpressed and the pathway hyperactivated in breast cancer. Consistent with our findings, NEDDylation is positively correlated with poor prognosis in different cancers 7,35,36 .…”

Proteomics identifies neddylation as a potential therapy target in small intestinal neuroendocrine tumors

“…As an example it has been shown that high expression of RBX1 is coupled to poor prognosis in gastric cancer [25], bladder cancer [26], and non-small cell lung cancer [27]. Similarly, NEDD8 overexpression has been coupled to poor prognosis in hepatocellular carcinoma [28] and bladder cancer [29], and increased levels of neddylated Cullin-1 has previously been shown in high-grade lung NETs [30]. Also in nasopharyngeal carcinoma, overexpression of NEDD8 was coupled to shorter overall survival [31] and in the same publication it was also shown in cell line models that suppression of NEDD8 levels directly inhibits cell growth.…”

NEDD9 overexpression: Prognostic and guidance value in acute myeloid leukaemia

“…5,10,11 Oncogenic role of NEDD8 has been demonstrated in diverse human cancers. 6,[12][13][14] Notably, NEDD8-activating enzyme inhibitor MLN4924 (pevonedistat) has been used in clinical treatment of AML. 6,[15][16][17] NEDD9, as a member of the CAS family of adhesion docking proteins, plays a key role in regulating several signalling cascades related to multiple activities, including migration, adhesion, cell death or proliferation.…”