Human TRAF6 ELISA Matched Antibody Pair

Tumor necrosis factor receptor-associated factor 6 (TRAF6) has been found to be involved in carcinogenesis in multiple cancers. However, the precise role of TRAF6 in cancer has not been extensively investigated and remains largely unknown. In this study, we aimed to investigate the biological function of TRAF6 and its underlying molecular mechanisms in cancer. A positive correlation between poor tumor differentiation and TRAF6 expression status was observed in both oral cancer and breast cancer. Overexpression of TRAF6 promoted proliferation, migration, and G(0)/G(1) to S phase transition in tumor cells. Tumor necrosis factor receptor-associated factor 6-mediated AKT ubiquitination and subsequent phosphorylation played an essential role in the control of tumor cell malignant behavior. In vivo treatment with TRAF6, but not the E3 ligase deficient TRAF6 mutant, facilitated tumor growth. Our findings indicate that TRAF6 contributes to malignant behavior of human cancers through promoting AKT ubiquitination and phosphorylation. Therefore, TRAF6 could serve as a therapeutic target in cancers.

Identifying regulatory mechanisms that influence inflammation in metabolic tissues is critical for developing novel metabolic disease treatments. Here, we investigated the role of microRNA-146a (miR-146a) during diet-induced obesity in mice. miR-146a is reduced in obese and type 2 diabetic patients and our results reveal that miR-146a-/- mice fed a high-fat diet (HFD) have exaggerated weight gain, increased adiposity, hepatosteatosis, and dysregulated blood glucose levels compared to wild-type controls. Pro-inflammatory genes and NF-B activation increase in miR-146a-/- mice, indicating a role for this miRNA in regulating inflammatory pathways. RNA-sequencing of adipose tissue macrophages demonstrated a role for miR-146a in regulating both inflammation and cellular metabolism, including the mTOR pathway, during obesity. Further, we demonstrate that miR-146a regulates inflammation, cellular respiration and glycolysis in macrophages through a mechanism involving its direct target Traf6. Finally, we found that administration of rapamycin, an inhibitor of mTOR, was able to rescue the obesity phenotype in miR-146a-/- mice. Altogether, our study provides evidence that miR-146a represses inflammation and diet-induced obesity and regulates metabolic processes at the cellular and organismal levels, demonstrating how the combination of diet and miRNA genetics influences obesity and diabetic phenotypes. Author summary Obesity and metabolic disease are on the rise throughout the world, creating a need for research into the interaction between diet and genetics. It is known that chronic inflammation contributes to obesity, but it is not well understood how inflammation and inflammatory genes are controlled to prevent obesity. Here we found that a specific microRNA, miR-146a, controls inflammation and prevents obesity onset when mice are fed a high-fat diet. In the absence of miR-146a, mice become obese and develop diabetic symptoms in a diet-dependent manner. We found that miR-146a is highly expressed in immune cells and regulates the inflammatory function of macrophages within fat tissue. Within macrophages, we identified metabolic pathways regulated by miR-146a that could contribute to its protective role during DIO, and show that blockade of mTOR using rapamycin could reverse the obesity phenotype in miR-146a-/- mice. Human studies have previously shown that miR-146a expression is decreased in obese and diabetic patients, and our work suggests that miR-146a is mechanistically involved in the development of obesity and therefore can be a potential therapeutic target. Taken together, our work demonstrates that miRNA genetics and lifestyle are both important, contributing factors to diet-induced metabolic disease.