No abstract

Activation of YAP/TEAD signaling is very common in the progression of HCC (Hepatocellular carcinoma). Nuclear pore complex (NPC) regulates the shuttling of proteins between cytoplasm and nucleus. Nuclear accumulation of YAP protein has been observed in the majority of HCC tissues. However, whether NPC could regulate the YAP/TEAD signaling remains unknown. In this study, it was found NUP37, the component of NPC, significantly up-regulated in HCC clinical samples and mouse model. Over-expression of NUP37 promoted the growth, migration and invasion of HCC cells, while knocking down the expression of NUP37 inhibited the growth, migration, invasion and metastasis of HCC cells and improved the survival of the mouse model. NUP37 interacted with YAP and activated YAP/TEAD signaling by enhancing the interaction between YAP and TEAD. Taken together, these data demonstrated the oncogenic roles of NUP37 in the progression of HCC and suggested that NUP37 might be a promising therapeutic target.

Neuroprotective effect of propofol against cerebral ischemia injury was widely investigated. However, its mechanisms remain unclear. Phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway is supposed as a cell survival pathway, and phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a negative regulator of AKT phosphorylation. Whether PTEN was involved in the protective effect of propofol against cerebral ischemia injury was not elucidated. In this study, the function of PTEN in the acute phase of cerebral ischemia injury was investigated. Our data showed that propofol promoted the PTEN degradation in the acute phase of cerebral ischemia injury and concurrently activated AKT phosphorylation. The increase of ubiquitinated PTEN caused by cerebral ischemia injury were degraded in propofol-pretreated rats. Moreover, we evidenced that proteasome activity was stimulated in propofol-treated rats. These data pointed that PTEN degradation was facilitated in the acute phase after propofol treatment possibly through activating ubiquitin-proteasome system. Therefore, we applied PTEN inhibitor-bpV before cerebral ischemia injury. Like propofol, bpV pretreatment also mitigated cerebral ischemia injury-induced cell loss in CA1 region and memory impairment. Taken together, our data suggest that PTEN degradation is neuroprotective against cerebral ischemia injury and propofol facilitates PTEN degradation to prevent hippocampal neuronal loss and memory deficit in cerebral ischemia injury.