Silencing of OTUB1 inhibits migration of human glioma cells in vitro.

OTU domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1) protein, a deubiquitinating enzyme (DUB) which belongs to the ovarian tumor (OTU) family, was reported to be associated with the development of various malignancies. However, the potential function of OTUB1 in human gliomas was still unclear. In this study, we sought to investigate the function of OTUB1 in the pathological process of gliomas and analyze its related clinical significance. Western blot and immunohistochemistry analyses demonstrated that OTUB1 was overexpressed in glioma tissues, and statistical analysis suggested the expression level of OTUB1 was significantly correlated with the WHO grades of human gliomas (P < 0.05). Moreover, Kaplan-Meier curve also indicated that high expression of OTUB1 was correlated with a poor prognosis. In vitro, silencing OTUB1 retarded the migration ability of glioma cells. Knockdown of OTUB1 increases epithelial-mesenchymal transition-related protein E-cadherin expression, but decreases simultaneously the expression of vimentin and snail. Furthermore, down-regulated expression of OTUB1 also resulted in decreased expression of some extracellular matrix degradation-related proteins, such as matrix metallopeptidase (MMP)2 and MMP9. All results suggested that OTUB1 was a valuable marker in the pathogenesis of human gliomas and could be used as a novel biomarker for glioma therapy in the future.

Overexpression of NIMA-related kinase 6 (NEK6) contributes to malignant growth and dismal prognosis in Human Breast Cancer.

NIMA Related Kinase 6 (Nek6) is a protein kinase involved in various cellular processes, including cell cycle regulation, apopotosis, senescence, telomere maintainance and chemoresistance. In the present study, we investigated the role of Nek6 in breast tumorigenesis and the prognostic merit of Nek6 expression in breast cancer. Immunohistochemistry and Western blot analyses was conducted to determine the expression profile of Nek6 in 133 breast cancer specimens. Nek6 was overexpressed in a majority of breast cancer specimens, compared with the adjacent non-tumorous tissues. Furthermore, we revealed that high expression of Nek6 was associated with histologic grade, tumor size and TNM stage in breast cancer. Liner regression analysis showed a significant association between the levels of Nek6 and Ki-67. Cox regression analysis indicated that Nek6 expression was an independent prognostic predictor for breast cancer. Moreover, intracellular level of Nek6 was remarkably increased following the release from serum starvation in MCF-7 cells. EdU incorporation assay indicated that depletion of Nek6 remarkably impaired the proliferation of MCF-7 cells. Finally, spheroid formation assay revealed that interference of Nek6 led to diminished oncospheroid-forming capacity of breast cancer cells. In conclusion, our results imply that Nek6 plays a facilitating role in breast cancer cell proliferation and may serve as a promising therapeutic target for breast cancer.

PSMB4 overexpression enhances the cell growth and viability of breast cancer cells leading to a poor prognosis.

PSMB4, proteasome subunit ß4, is a member of the ubiquitin-proteasome family, and is elevated in a variety of malignancies. However, the expression level and related mechanism of PSMB4 in breast cancer remains unclear. Therefore, the present study investigated the expression level of PSMB4 in eight pairs of breast cancer and adjacent normal tissues. In addition, the relationship between the expression of PSMB4 and the clinical data of 92 breast cancer patients was discussed. First, it was found that PSMB4 expression was obviously upregulated in breast cancer tumor tissues and cell lines (MDA-MB-231 and MCF-7), and its level was significantly associated with tumor grade (P=0.005), tumor size (P=0.047), Ki-67 expression (P=0.040) and the poor prognosis of breast cancer. The present results demonstrated that PSMB4 could promote the proliferation of breast cancer cells, and was positively correlated with the expression of PCNA using an in vitro starvation-refeeding experiment. In addition, PSMB4­siRNA transfection assay suggested that PSMB4 knockdown can decrease NF-κB activity and cell viability, and result in cell cycle arrest at the G1/S phase. These findings revealed that PSMB4 might facilitate breast cancer progression by promoting cell proliferation and viability. In summary, PSMB4 may be recognized as an efficacious prognostic marker and potential therapeutic target for breast cancer.

High expression of PIWIL2 promotes tumor cell proliferation, migration and predicts a poor prognosis in glioma.

Piwi-like RNA-mediated gene silencing 2 (PIWIL2), has been reported as an oncogene tightly associated with the genesis and progression of various malignancies. Nevertheless, the function of the PIWIL2 protein in human gliomas has not yet been clarified. In this study, we sought to investigate the clinical significance of PIWIL2 expression and reveal its function in the pathological process of gliomas. Through western blot and immunohistochemical analyses we found that PIWIL2 was overexpressed in glioma tissues. Moreover, the expression level of PIWIL2 was also significantly correlated with the WHO grades of human gliomas and Ki-67 expression. Kaplan­Meier curves indicated that PIWIL2 was a prognostic factor for the survival of glioma patients and a high expression of PIWIL2 was correlated with a poor prognosis. In vitro, knockdown of PIWIL2 in glioma cells was shown to induce cell cycle arrest and increase apoptosis. Furthermore, silencing of PIWIL2 expression also obviously suppressed the migration of glioma cells. All the results demonstrated that PIWIL2 plays a significant role in the pathogenesis of human gliomas and may be used as a potential diagnostic marker and a therapeutic target of glioma in the future.