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Recently, calcyclin-binding protein or Siah-1-interacting protein (CacyBP/SIP), a component of a novel ubiquitinylation pathway, could regulate the b-catenin degradation (Fukushima et al., Immunity 2006, 24, 29 -39). However, the potential role of CacyBP/SIP itself in human glioma cells has not been clarified. Here, we found that CacyBP/SIP was expressed highly in human glioma tissues. Silencing of CacyBP/SIP by short-hairpin RNA severely suppressed the proliferation of human glioma cell U251, which was at least partly mediated by downregulation of phospho-Akt (p-Akt) and phospho-b-catenin (p-b-catenin) as well as upregulation of p53 and p21. Furthermore, overexpression of CacyBP/SIP obviously promoted the proliferation of human glioma U251, which exhibited the exactly contrary trend in the expression of p-Akt, p-b-catenin, p53, and p21. Taken together, these findings suggest that CacyBP/SIP plays important roles in the proliferation of human glioma cell which might be involved in the development of human glioma. V C 2014 IUBMB Life, 66(4): [286][287][288][289][290][291] 2014

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It has been reported that by regulating PHD3 stability, Siah1 contributes to the abundance of hypoxia-inducible factor (HIF)-1α, thereby playing an important role in the cellular response to hypoxia. However, the expression level and functional significance of Siah1 in human malignant glioma, which is characterized by high migration and invasion potential, have never been investigated. We report here, that Siah1 was expressed highly in human glioma tissues compared with its expression in normal brain tissues and was correlated with advanced tumor status and stage. The knockdown of Siah1 by short-hairpin RNA severely suppressed the migration and invasion of human glioma U251 cells under hypoxia, while overexpression of Siah1 promoted it. Furthermore, we demonstrated that the glioma cell migration and invasion under hypoxia mediated by Siah1 was achieved by reducing the stability of PHD3, which protected the HIF-1α from degradation. These findings suggest that Siah1 plays important roles in the migration and invasion of human glioma cells under hypoxia, which may provide some guidance for the targeted therapy of human glioma based on the interference of the Siah1-PHD3-HIF-1α signaling pathway.