NEDD4 E3 ubiquitin protein ligase serves an important role in cutaneous melanoma occurrence and development

Abstract

The present study aimed to discuss the effects and relative mechanisms of NEDD4 E3 ubiquitin protein ligase (NEDD4) in cutaneous melanoma (CMM) occurrence and development. Clinical cancer and adjacent normal tissues samples were collected to analyze pathological changes and protein expression of NEDD4. Moreover, small interfering (si)RNA was used to knockdown NEDD4 expression in SK-MEL-2 and Malme-3M cells. Cellular proliferation, apoptosis, invasiveness and migration were examined using colony formation, flow cytometric, Transwell and wound-healing assays, respectively. In addition, the relative mRNA and protein expression levels of NEDD4, notch receptor 1 (Notch1) and PTEN were evaluated via reverse transcription-quantitative (RT-q) PCR and western blotting. It was found that NEDD4 mRNA and protein expression were significantly upregulated (both P<0.01). Following NEDD4-knockdown, colony number was significantly decreased, while the apoptotic rate was significantly increased, the invasive cell number was significantly inhibited and the wound-healing capacity was significantly decreased. Following si-NEDD4 transfection, RT-qPCR and western blotting revealed that NEDD4 and Notch1 mRNA and protein expression levels were significantly downregulated, while those of PTEN were significantly upregulated in the SK-MEL-2 and Malme-3M cell lines. Collectively, the current results suggest that NEDD4-knockdown effectively suppressed CMM biological activity by regulating the Notch1/PTEN pathway in vitro .

The Role of Ubiquitination and the E3 Ligase Nedd4 in Regulating Corneal Epithelial Wound Healing

“… 38 Several in vitro studies further corroborated the role of Nedd4 in promoting cell migration and proliferation. 39 – 41 Collectively, these findings underscore the significance of Nedd4 as a central player in the wound healing processes, extending beyond the corneal epithelium to other tissue types.…”