ABSTRACT
IL-6 signaling plays a crucial role in the survival and metastasis of skin cancer. NEDD4L acts as a suppressor of IL-6 signaling by targeting GP130 degradation. However, the effects of the NEDD4L-regulated IL-6/GP130 signaling pathway on skin cancer remain unclear. In this study, protein expression levels of NEDD4L and GP130 were measured in tumor tissues from patients with cutaneous squamous cell carcinoma. Skin tumors were induced in wild-type and Nedd4l-knockout mice, and activation of the IL-6/GP130/signal transducer and activator of transcription 3 signaling pathway was detected. The results indicated a negative correlation between the protein expression levels of NEDD4L and GP130 in cutaneous squamous cell carcinoma tissues from patients. Nedd4l deficiency significantly promoted 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate-induced skin tumorigenesis and benign-to-malignant conversion by activating the IL-6/GP130/signal transducer and activator of transcription 3 signaling pathway, which was abrogated by supplementation with the GP130 inhibitor SC144. Furthermore, our findings suggested that NEDD4L can interact with GP130 and promote its ubiquitination in skin tumors. In conclusion, our results indicate that NEDD4L could act as a tumor suppressor in skin cancer, and inhibition of GP130 could be a potential therapeutic method for treating this disease.
ABSTRACT
Microplastic pollution is ubiquitous in the marine environment and the consumption of shellfish containing microplastics may pose a risk to human health. This study investigated the occurrence and characteristics of microplastics in three commonly consumed shellfish in the coastal region of Jiangsu Province, China. The average abundance of microplastics in shellfish varied from 0.33 to 9.33 items/individual (0.06-0.92 items/g, wet weight of soft tissue). Microplastic abundance in Jiangsu was relatively low compared to studies from other regions of China and worldwide. Synthetic fibers (66.20%) were predominant and included rayon (34.84%) and polyester (23.23%), indicating that the majority of particles originated from the discharge of clothing fibers in domestic sewage. Transparent (66.20 %) particles were the most common, particle size was generally less than 500 µm (62.30%), and abundance decreased as the particle size increased. The average annual intake of microplastics by Jiangsu coastal residents via the consumption of common bivalves was estimated to be 1088.64 items/person/year. This study provides data to support ecological and health risk assessments for microplastics in the Jiangsu coastal region.
