Anti-FBXW2 monoclonal antibody Made to order

Renal cell carcinoma is one of the most common urinary system tumors in adults, it is usually asymptomatic in its early stage and the patients are often diagnosed late. MicroRNA has a higher diagnostic accuracy than traditional markers and may become a new type of early diagnostic biomarker for kidney cancer. Three computational methods and several bioinformatic methods including PPI network, overall survival analysis and enrichment analysis were used to identify the significant differentially expressed miRNAs. Thirteen miRNAs that were significantly differentially expressed in RCC patients were identified, 10 of them have been proved to be associated with kidney cancer in other studies, miR-576, miR-616 and miR-133a-2 are three newly discovered biomarkers of RCC in this study. We found that the target genes of miR-576 (CUL3 and RAC1) are involved in the regulation of multiple cancer-related biological pathways, and the target gene of miR-616 (ASB13 and FBXW2) has been reported to be associated with the development of other cancers. Our findings may have guiding significance for the early diagnosis of renal cell carcinoma.

Chronic low-grade inflammation orchestrated by macrophages plays a critical role in metabolic chronic diseases, like obesity and atherosclerosis. However, the underlying mechanism remains to be elucidated. Here, the E3 ubiquitin ligase F-box/WD Repeat-Containing Protein 2 (FBXW2), the substrate-binding subunit of E3 ubiquitin ligase SCF (a complex of FBXW2, SKP1, and cullin-1), as an inflammatory mediator in macrophages, is identified. Myeloid-specific FBXW2 gene deficiency improves both obesity-associated with insulin resistance and atherosclerosis in murine models. The beneficial effects by FBXW2 knockout are accompanied by decreased proinflammatory responses and macrophage infiltration in the microenvironment. Mechanistically, it is identified that KH-type splicing regulatory protein (KSRP) is a new bona fide ubiquitin substrate of SCFFBXW2. Inhibition of KSRP prevents FBXW2-deficient macrophages from exerting a protective effect on inflammatory reactions, insulin resistance and plaque formation. Furthermore, it is demonstrated that the C-terminus (P3) of FBXW2 competitively ablates the function of FBXW2 in KSRP degradation and serves as an effective inhibitor of obesity and atherogenesis progression. Thus, the data strongly suggest that SCF(FBXW2)is an important mediator in the context of metabolic diseases. The development of FBXW2 (P3)-mimicking inhibitors and small-molecular drugs specifically abrogating KSRP ubiquitination-dependent inflammatory responses are viable approaches for obesity and atherosclerosis treatment.