Background
Chemo-resistance is still considered one of the key factors in the mortality of ovarian cancer. In this work, we found that ubiquitin-conjugating enzyme E2 N (UBE2N) is downregulated in paclitaxel-resistant ovarian cancer cells. It suggests UBE2N to be critical in the regulation of paclitaxel sensitivity in ovarian cancer.
Materials and Methods
Ovarian cancer cells with stably overexpressed UBE2N were injected into nude mice to assess tumor growth and paclitaxel sensitivity in vivo. The MTT assay was applied to observe the effect of UBE2N expression on paclitaxel sensitivity. A real-time PCR array, specific for human cancer drug resistance, was used to examine the potential downstream target genes of UBE2N. The expression of UBE2N and potential downstream target genes was determined by Western blotting. The analysis of Gene Ontology and protein–protein interactions of these differentially expressed genes (DEGs) was performed using online tools. To evaluate the prognostic value of hub genes expression for ovarian cancer patients treated with paclitaxel, we applied the online survival analysis tool.
Results
Overexpressed UBE2N enhanced the paclitaxel sensitivity of ovarian cancer cells in vitro and in vivo. Thirteen upregulated DEGs and 11 downregulated DEGs were identified when we knockdown UBE2N. Meanwhile, 9 hub genes with a high degree of connectivity were selected. Only Fos proto-oncogene, AP-1 transcription factor subunit (Fos), was overexpressed upon decreasing UBE2N levels, indicating a poor outcome for patients treated with paclitaxel. Moreover, reduced UBE2N could increase Fos expression and reduce P53. Furthermore, reversed regulation of Fos and P53 based on UBE2N reduction could reverse paclitaxel sensitivity, respectively.
Conclusion
Our study suggests that UBE2N could be used as a therapeutic agent for paclitaxel-resistant ovarian cancer through Fos/P53 pathway. Further studies are needed to elucidate the specific mechanism.
SF6/CF4 mixture is considered a potential substitution for SF6 in gas-insulated equipment owing to the considerable insulation and low temperature characteristics of CF4. This paper concerns the substitutability of the mixture on the surface flashover property. Epoxy resin composites for solid insulators are applied since flashover at the insulator interface often occurs and results in severe damage to the safe operation of the equipment. Two kinds of electrode systems are designed to study DC flashover properties with different electric field uniformities. The obtained result shows that the flashover voltage in the 20% SF6/80% CF4 mixture achieved more than 70% of the voltage in SF6 at the same pressure. The mixture shows considerable synergy in the surface flashover process and performed different tendencies with varying gas pressures and contents under different electrode systems due to the influence of surface accumulated charge. Moreover, it is considered that surface charge due to ionization may result in a reversal phenomenon for voltage polarity with increasing pressure. The results indicate the possibility of SF6/CF4 functioning as an efficient substitution of SF6 with a considerable insulation property and improved environmental protection characteristics.
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