Gastric cancer (GC) is one of the most common malignant cancers worldwide. Metastasis leads to poor prognoses in GC patients in advanced stages. Our previous studies have demonstrated that JWA functions as a tumour suppressor and that low expression of JWA in GC tissues is significantly correlated with shorter overall survival (OS) as well as with advanced clinicopathologic features in patients. However, the mechanism of dysregulation of JWA in cancers is not clear. In the present study, we found that an E3 ubiquitin ligase, RNF185, directly interacted with JWA and promoted its ubiquitination at the K158 site, resulting in subsequent degradation. Moreover, the protein level of RNF185 was negatively correlated with JWA in tumour tissues from GC patients. High RNF185 expression was significantly correlated with shorter OS. Additionally, increased RNF185 expression facilitated GC cell migration in vitro and promoted GC metastasis in vivo by downregulating JWA expression. However, this effect was reversed by replenishment of JWA. In conclusion, our findings highlight the following: (1) RNF185 promotes GC metastasis by mediating JWA degradation via a ubiquitin-proteasome pathway; (2) the K158 site of JWA is essential for its ubiquitination in GC cells. These findings suggest that RNF185 is a novel candidate prognostic marker and potential therapeutic target for GC.
Expected returns, variances, and co-variances are key inputs of mean-variance portfolio selection problems. In traditional mean-variance portfolio models, the model uncertainty is excluded a priori. But in practice, these parameters are not known a priori and are usually estimated with error. Current researches incorporate the model uncertainty into the mean-variance framework but mainly focus on the uncertain means. The aim of this dissertation is to incorporate uncertain variance-covariance into mean-variance portfolio model via the concept of ambiguity and ambiguity aversion. The approaches developed in this study numerically compare the impact from return ambiguity and variance ambiguity. In particular, re-examine if uncertain variance-covariance can lead to "No-Participation in Stock Market" and/or "Home Bias" via stock indexes data.
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