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Background: Epithelial ovarian cancer (OC) is the fourth leading cause of cancer-related deaths in women, with a 5-year survival rate of 30%-50%. Platinum resistance is the chief culprit for the high recurrence and mortality rates. Several studies confirm that the metabolic regulation of ubiquitinating enzymes plays a vital role in platinum resistance in OC. Methods: In this study, we selected ubiquitin-conjugating enzyme E2S (UBE2S) as the candidate gene for validation. The levels of UBE2S expression were investigated using TCGA, GTEx, UALCAN, and HPA databases. In addition, the correlation between UBE2S and platinum resistance in OC was analyzed using data from TCGA. Cisplatin-resistant OC cell lines were generated and UBE2S was knocked down; the transfection efficiency was verified. Subsequently, the effects of knockdown of UBE2S on the proliferation and migration of cisplatin-resistant OC cells were examined through the CCK8, Ki-67 immunofluorescence, clone formation, wound healing, and transwell assays. In addition, the UBE2S gene was also validated in vivo by xenograft models in nude mice. Finally, the relationship between the UBE2S gene and autophagy and the possible underlying regulatory mechanism was preliminarily investigated through MDC and GFP-LC3-B autophagy detection and western blotting experiments. Most importantly, experimental validation of mTOR agonist reversion (the rescuse experiments) was also performed. Results: UBE2S was highly expressed in OC at both nucleic acid and protein levels. The results of immunohistochemistry showed that the level of UBE2S expression in platinum-resistant samples was significantly higher relative to the platinum-sensitive samples. By cell transfection experiments, knocking down of the UBE2S gene was found to inhibit the proliferation and migration of cisplatin-resistant OC cells. Moreover, the UBE2S gene could inhibit autophagy by activating the PI3K/AKT/mTOR signaling pathway to induce cisplatin resistance in OC in vivo and in vitro. Conclusion: In conclusion, we discovered a novel oncogene, UBE2S, which was associated with platinum response in OC, and examined its key role through bioinformatics and preliminary experiments. The findings may open up a new avenue for the evaluation and treatment of OC patients at high risk of cisplatin resistance. [ABSTRACT FROM AUTHOR]

According to the 2020 GLOBOCAN Global Cancer Women's Cancer Data, ovarian cancer is the eighth most common tumor in humans. Still, its mortality rate ranks first among all gynecological tumors, with a 5-year survival rate of 30% to 50%. Widespread clinical use of platinum-based drugs has improved survival outcomes in patients with ovarian cancer, but organ toxicity and drug resistance hinder their anticancer effects. In particular, the resistance to platinum drugs is an important reason for ovarian cancer's high recurrence rate and mortality. With the development of chemotherapeutic drugs synthesized by nanomaterials in the biomedical field, we developed bifunctional ultrafine polyethyleneimine caged platinum nanoclusters (PEI-Pt NCs) to improve the dilemma of platinum drugs. This study aimed to elucidate the antitumor effect of PEI-Pt NCs in OC. First, as observed by confocal microscopy, Pt NCs entered OC cells in a dose-dependent manner and accumulated on the surface of the nuclear membrane and in the nucleus. Subsequently, through cck8, ki-67 immunofluorescence, wound healing assay, transwell assay, clone formation assay, flow cytometry, tunel staining, and western blotting assay, it was confirmed that PEI-Pt NCs could inhibit the proliferation and migration and induce the apoptosis of ovarian cancer cells. PEI-Pt NCs can be used as fluorescent markers for systemic bioimaging of ovarian cancer, showing great potential in diagnosing and treating ovarian cancer, and making a specific contribution to solving the dilemma of platinum-based drug therapy for OC. [ABSTRACT FROM AUTHOR]