According to a study, published in Experimental & Molecular Medicine, the neuronally expressed developmentally downregulated 4 (NEDD4) gene has been implicated with tumor growth in various cancers. To determine if this association is present in bladder cancer, Minghuan Mao, and colleagues examined the NEDD-4 mediated Kruppel-like factor 8/microRNA-132/nuclear factor E2-related factor 2 (KLF8/miR-132/NRF2) axis, and found correlations between NEDD4 and cancer development.
The study’s authors suggested that NEDD4 could be a “potential therapeutic target against tumor recurrence and metastasis” in patients with bladder cancer.
The trial included a total of 45 patients who underwent resection surgeries at the Fourth Affiliated Hospital of China Medical University. Tumor samples were taken after excision, and nonfunctional normal bladder tissue samples were taken during surgery to serve as controls.
According to the article, NEDD4 and KLF8 were overexpressed in bladder cancer tissue samples, and were both associated with poorer survival rates in patients. In cancer cells, the authors observed that NEDD4 “intensified the stability and transcriptional activity of KLF8 through ubiquitination to augment cell viability and migratory ability.” They assessed that NEDD4 promoted binding of KLF8 to the miR-132 promoter region and inhibited miR-132 expression, while KLF8 inhibited the expression of miR-132 to augment bladder cancer cells. Furthermore, miR-132 was seen to downregulate the expression of NRF2 and thereby restrict the viability and migratory ability of cancer cells.
Ultimately, the authors concluded that their in vivo results verified the role of NEDD4 in regulating the KLF8/miR-132/NRF2 axis by accelerating tumor growth and lung metastasis. Their study furthered the understanding of NEDD4’s association with development of tumors, and may indicate treatment targets for patients with bladder cancer.