Expression and correlation analysis of Skp2 and CBX7 in cervical cancer

AimsS-phase kinase-associated protein 2 (Skp2) oncoprotein is overexpressed in a variety of cancer tissues and promotes the malignant development of cancer. The expression levels of chromobox homolog 7 (CBX7) protein are varied among different types of cancer tissues, but its role in cervical cancer is not clear. We aimed to examine the expression and clinical significance of Skp2 and CBX7 proteins as well as their correlations in cervical cancer.MethodsImmunohistochemistry was used to detect the expression of Skp2 and CBX7 proteins in the cancerous tissues and adjacent tissues of 64 patients with cervical cancer. Relevant clinicopathological data of these patients were collected, compared and analysed for the correlations.ResultsThe expression of Skp2 protein in cervical cancer (87.5%) was higher than that in paracancerous tissues (14.1%), and the expression was positively correlated with clinical stage, malignant degree, lymphatic metastasis, vascular invasion and interstitial invasion. The expression of CBX7 protein in cervical cancer (48.4%) was lower than that in paracancerous tissues (96.8%), and the expression was negatively correlated with clinical stage, malignant degree, interstitial invasion, vascular invasion and lymphatic metastasis. The expression of Skp2 protein and CBX7 protein in cervical cancer tissues and adjacent tissues was negatively correlated. The expression of Skp2 and CBX7 proteins was closely related to the clinicopathological features of cervical cancer.ConclusionsCBX7 may play the role of a tumour suppressor gene in cervical cancer and provide reference value for the diagnosis and new targeted treatment of cervical cancer.

Histone Deacetylase Inhibitors Increase p27Kip1by Affecting Its Ubiquitin-Dependent Degradation through Skp2 Downregulation

Histone deacetylase inhibitors (HDACIs) represent an intriguing class of pharmacologically active compounds. Currently, some HDACIs are FDA approved for cancer therapy and many others are in clinical trials, showing important clinical activities at well tolerated doses. HDACIs also interfere with the aging process and are involved in the control of inflammation and oxidative stress.In vitro, HDACIs induce different cellular responses including growth arrest, differentiation, and apoptosis. Here, we evaluated the effects of HDACIs on p27Kip1, a key cyclin-dependent kinase inhibitor (CKI). We observed that HDACI-dependent antiproliferative activity is associated with p27Kip1accumulation due to a reduced protein degradation. p27Kip1removal requires a preliminary ubiquitination step due to the Skp2-SCF E3 ligase complex. We demonstrated that HDACIs increase p27Kip1stability through downregulation of Skp2 protein levels. Skp2 decline is only partially due to a reduced Skp2 gene expression. Conversely, the protein decrease is more profound and enduring compared to the changes of Skp2 transcript. This argues for HDACIs effects on Skp2 protein posttranslational modifications and/or on its removal. In summary, we demonstrate that HDACIs increase p27Kip1by hampering its nuclear ubiquitination/degradation. The findings might be of relevance in the phenotypic effects of these compounds, including their anticancer and aging-modulating activities.

Regulation of Skp2 Expression and Activity and Its Role in Cancer Progression

The regulation of cell cycle entry is critical for cell proliferation and tumorigenesis. One of the key players regulating cell cycle progression is the F-box protein Skp2. Skp2 forms a SCF complex with Skp1, Cul-1, and Rbx1 to constitute E3 ligase through its F-box domain. Skp2 protein levels are regulated during the cell cycle, and recent studies reveal that Skp2 stability, subcellular localization, and activity are regulated by its phosphorylation. Overexpression of Skp2 is associated with a variety of human cancers, indicating that Skp2 may contribute to the development of human cancers. The notion is supported by various genetic mouse models that demonstrate an oncogenic activity of Skp2 and its requirement in cancer progression, suggesting that Skp2 may be a novel and attractive therapeutic target for cancers.