最近的研究表明，自噬在妇科肿瘤中发挥着重要作用，自噬调控组分的泛素修饰是调控自噬的必要手段。在本研究中，我们发现UBE2C通过抑制自噬，影响子宫内膜癌细胞的凋亡和增殖。通过电子显微镜观察细胞超微结构和实验生化分析，发现UBE2C表达被抑制的癌细胞显示出典型的自噬特征。我们还通过联用自噬药物抑制剂氯喹和/或巴芬霉素A1处理细胞，使用mRFP-GFP-LC3监测自噬流量，并确定UBE2C是否抑制自噬程序。通过研究UBE2C抑制自噬的相应机制，发现UBE2C诱导K48-链接的SIRT1泛素化，促进SIRT1的泛素化依赖性降解，从而降低H4K16脱乙酰化水平，进而通过表观遗传学抑制自噬相关基因的表达。CCK-8、荧光染色和免疫荧光实验的结果进一步表明，删除与自噬相关的基因BECN1明显减轻UBE2C敲低诱导的细胞凋亡。此外，UBE2C的过表达在裸鼠异种移植模型中促进了肿瘤生长。然而，自噬激动剂雷帕霉素的介入成功逆转了UBE2C过表达介导的肿瘤生长和凋亡抑制。综上所述，我们的研究表明，UBE2C介导的SIRT1泛素化和降解通过表观遗传学抑制自噬而促进子宫内膜癌的恶性进展。意义：我们的研究突显了UBE2C在子宫内膜癌中的致癌作用和调控机制；UBE2C通过自噬相关机制抑制子宫内膜癌细胞的凋亡，我们的发现为治疗子宫内膜癌提供了新的思路。

Recent studies have shown that autophagy plays an important role in gynecological tumours, and ubiquitin modification of autophagy regulatory components is essential to regulate autophagic. In this study, we found that UBE2C affects endometrial cancer cell apoptosis and proliferation by inhibiting autophagy. Electron microscopy observation of cell ultrastructure and experimental biochemical analysis showed that EC cells with UBE2C expression knocked down display typical autophagic characteristics. Cells were cotreated with the autophagy pharmacological inhibitors chloroquine and/or bafilomycin A1, and mRFP-GFP-LC3 assays were performed to monitor autophagic flux and determine whether UBE2C suppresses the autophagy program. Investigation of the corresponding mechanism by which UBE2C inhibits autophagy revealed that UBE2C induces K48-linked SIRT1 ubiquitination and promotes ubiquitination-dependent degradation of SIRT1, subsequently reducing H4K16 deacetylation levels and epigenetically inhibiting the expression of autophagy-related genes. The results of CCK-8, Hoechst staining, and immunofluorescence assays further indicated that deletion of the autophagy-related gene BECN1 significantly attenuates UBE2C knockdown-induced cell apoptosis. Moreover, overexpression of UBE2C promoted tumor growth in the xenograft mice model. While, the introduction of rapamycin, an agonist of autophagy, successfully reversed tumor growth and apoptosis inhibition mediated by UBE2C overexpression in vitro and in vivo. Taken together, our results suggested that UBE2C-mediated ubiquitination and degradation of SIRT1 contribute to the malignant progression of endometrial cancer through epigenetic inhibition of autophagy. Implications: Our study highlights the tumorigenic role and regulatory mechanism of UBE2C in EC; UBE2C inhibits EC cell apoptosis through autophagy-related mechanisms and our findings provide new insights into the treatment of endometrial cancer.