PDZ-Binding Kinase-Dependent Transcriptional Regulation of CCNB2 Promotes Tumorigenesis and Radio-Resistance in Glioblastoma.

Increasing evidence has indicated that PDZ binding kinase (PBK) promotes proliferation, invasion, and therapeutic resistance in a variety of cancer types. However, the physiological function and therapy-resistant role of PBK in GBM remain underexplored. In this study, PBK was identified as one of the most therapy-resistant genes with significantly elevated expression level in GBM. Moreover, the high expression level of PBK was essential for GBM tumorigenesis and radio-resistance both in vitro and in vivo. Clinically, aberrant activation of PBK was correlated with poor clinical prognosis. In addition, inhibition of PBK dramatically enhanced the efficacy of radiation therapy in GBM cells. Mechanically, PBK-dependent transcriptional regulation of CCNB2 was critical for tumorigenesis and radio-resistance in GBM cells. Collectively, PBK promotes tumorigenesis and radio-resistance in GBM and may serve as a novel therapeutic target for GBM treatment.

Dynamic expression of the suppressor of cytokine signaling-3 and cytokines in the cerebral basilar artery of rats with subarachnoid hemorrhage, and the effect of acetylcholine.

BACKGROUND: There are complex interactions between acetylcholine (ACh), the suppressor of cytokine signaling-3 (SOCS-3), and cytokines, however, little is known about their dynamic expression or their effects on cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). Therefore, we aimed to describe and clarify the dynamic expression of SOCS-3 and cytokines after SAH, as well as the relationships between the levels of SOCS-3, cytokines, and ACh. METHODS: The rat model of single cisterna magna injection was used to mimic acute SAH. The degree of CVS was indicated by lumen diameter and artery wall thickness under H&E staining. A semi-quantitative immunohistochemical analysis method was used to clarify the role of SOCS-3 in the CVS after SAH. We also measured the content of IL-6 and IL-10 in cerebrospinal fluid. RESULTS: We found that SOCS-3 expression levels increased rapidly within 12 h after SAH, more slowly after 12 h, and did not reach a peak within 48 h. Interleukin 6 (IL-6) levels rapidly increased within 24 h after SAH, reached a peak 24 h after SAH, and decreased slightly at 48 h. IL-10 levels increased during the first 6 h after SAH, after which this increase tapered off. ACh treatment reduced IL-6 levels and resulted in elevated levels of SOCS-3, but had no effect on IL-10 expression. Furthermore, ACh treatment relieved basilar arterial vasospasm, whereas mecamylamine pretreatment counteracted the activity of ACh. CONCLUSIONS: Taken together, these data indicate that SOCS-3 was involved in vasospasm via an IL-6- and IL-10-related mechanism, and that CVS following SAH could be reversed by the intraventricular injection of ACh.