Overexpression of immunoproteasome low-molecular-mass polypeptide 7 and inhibiting role of next-generation proteasome inhibitor ONX 0912 on cell growth in glioma.

Objectives: The aim of this study was to determine the expression level of immunoproteasome and its clinical significance in glioma preliminarily. Furthermore, we studied the function and molecular mechanism of proteasome inhibitor ONX 0912 on glioma cell. Materials and methods: The expression of immunoproteasome in glioma and tumor-adjacent brain tissues was detected by western blot. Immunohistochemical technique was used to detect the expression of low-molecular-mass polypeptide 7 in 55 cases of glioma tissues and 6 cases of tumor-adjacent brain tissues. Chi-square test was used to analyze the relationship between the expression level of low-molecular-mass polypeptide 7 and clinical characteristics. Kaplan-Meier method and Cox regression analysis were applied to analyze the correlation between low-molecular-mass polypeptide 7 expression and prognosis of patients. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium) (MTS) proliferation assay was introduced to detect the impact of ONX 0912 on proliferation of glioma cells. Western blot was used to detect the apoptosis- and autophagy-related protein in glioma cell treated with ONX 0912. Results: Our results showed that only low-molecular-mass polypeptide 7 expression was notably upregulated in gliomas in comparison with tumor-adjacent brain tissues and further increased in malignant gliomas compared with benign gliomas (P < 0.01). In the multivariate Cox proportional regression analyses, it was evident that low-molecular-mass polypeptide 7 was an independent unfavorable prognostic factor (P < 0.05). The results of MTS assay showed that ONX 0912 could inhibit the proliferation of glioma cell. Besides, we found that ONX 0912 could prompt apoptosis and autophagosome accumulation, which may be responsible for inhibiting glioma cell proliferation. Conclusion: In conclusion, our results indicated that low-molecular-mass polypeptide 7 might be a candidate prognostic biomarker, and proteasome inhibitor ONX 0912 might act as a potential treatment agent for glioma.