Background: Endometrial cancer (EC) is the most common gynecological malignancy with high incidence of metastasis, while the mechanism of metastasis in EC is not clear. Methods: Immunohistochemistry and real-time PCR assays were used to assess expression of SOX17 in paraffin-embedded tissues from EC patients and in EC cells. The migration of EC cells was assessed by wound-healing and Transwell assays as well as in an in vitro study of nude mice. In addition, the expression of specific proteins was analyzed by Western blot. Results: We observed that SOX17 expression levels were relatively high in stage I EC specimens, and were significantly correlated with the epithelial cadherin (E-cadherin) and β-catenin expression. Additionally, stage II EC patients whose specimens had relatively high SOX17 expression levels had better outcomes. Wound-healing and Transwell assays and in vivo murine experiments revealed that SOX17 inhibited EC cell migration. Meanwhile, SOX17 increased expression of E-cadherin and decreased expression of β-catenin and proteins in the Wnt signaling pathway. Moreover, LiCl (β-catenin activator) enhanced the regulatory effects of SOX17 on the expression of E-cadherin, promigratory cadherin, vimentin, and proteins in the Wnt signaling pathway, while XAV93920 (β-catenin inhibitor) exerted the opposite effect. The SOX17 N-terminus was proved to be necessary for these effects. Mechanistic investigations suggested SOX17 inhibits EC cell migration by inactivating the Wnt/β-catenin–epithelial mesenchymal transition (EMT) axis in EC cells. Conclusion: We uncovered a common SOX17–β-catenin–EMT mechanism underlying EC cell migration.

Endometrial cancer (EC) is the most common form of malignant gynecological tumor. Treatment with cisplatin (CDDP) is the mainstay of EC chemotherapy. The apoptotic machinery is regarded as an important etiological factor in chemoresistance. Recent evidence has suggested that overexpression of the transcription factor SOX17 prevented apoptosis in tumor cell lines. The effect of SOX17 on apoptosis in EC cisplatin chemoresistance remains unclear. Immunohistochemistry and the reverse transcription-polymerase chain reaction were employed to detect gene expression in paraffin-embedded EC tissues and blood samples. The anti-proliferative ability of SOX17 on EC cells was assessed by MTT. Flow cytometric analysis was used to detect cell apoptosis by annexin V/PI double-staining. The expression of apoptosis-related proteins was analyzed by western blot. In the in vivo study, nude mice were subcutaneously injected with EC cells, and received cisplatin treatment through intraperitoneal chemotherapy. Apoptosis of in vivo samples was analyzed by TUNEL assay. SOX17 expression decreased the chemical resistance of EC cells to CDDP. HEC-1B cells with an elevated expression of SOX17 had a lower cell viability and higher apoptosis rate after cisplatin exposure. Overexpression SOX17 up-regulated wild type p53 after being exposed to cisplatin, while the expression of BCL2-associated X protein and cleaved caspase-3 simultaneously increased. Caspase-9 inhibitor reduced the efficacy of SOX17 in HEC-1B cells after cisplatin treatment. In the in vivo study, SOX17 overexpression clearly restrained the tumor growth and increased the cisplatin toxicity and apoptosis of tumor cells. SOX17 is involved in the p53-mediated apoptosis pathway, and increases the sensitivity of HEC-1B cells to cisplatin.

The molecular mechanisms by which uterine leiomyoma (UL) cells proliferate are unclear. Long noncoding RNA (lncRNA) is reported to participate in the occurrence and development of gynecological cancers. We investigated the molecular mechanisms that lncRNA uses in UL. We found that lncRNA Alu-mediated p21 transcriptional regulator (APTR) showed higher expression in UL tumor tissues compared with that in normal uterine tissues. APTR induced cell proliferation and colony formation both in vitro and in vivo. The JASPAR database showed that APTR was likely interacted with ERα, and these molecules were identified via laser scanning confocal microscopy and RNA immunoprecipitation analysis. To verify the correlation between APTR and ERα, we overexpressed and underexpressed APTR and simultaneously expressed ERα. The results showed that APTR function was suppressed. APTR increased the expressions of the proteins in the Wnt pathway, and inhibiting ERα eliminated these responses. In conclusion, our data suggest that APTR promoted leiomyoma cell proliferation through the Wnt pathway by targeting ERα, suggesting a new role of APTR in the Wnt signaling pathway in UL.

Cuproptosis is the most recently discovered mode of cell death. It could affect the metabolism of cancer cells and surrounding infiltrating immune cells. In recent years, many studies have also shown that the tumor microenvironment (TME) plays a critical role in tumor growth and development. Mounting evidence suggests that Cuproptosis would bring unique insights into the development of pharmacological and nonpharmacological therapeutic techniques for cancer prevention and therapy. However, no study has been done on the combination of cuproptosis and TME in any cancer. Herein, we investigated the relationship between cuproptosis-related genes (CRGs), TME, and the prognosis of patients with Uterine Corpus Endometrial Carcinoma (UCEC). We identified three CRGs clusters based on 10 CRGs and three CRGs gene clusters based on 600 differentially expressed genes (DEGs) with significant prognostic differences. Following that, the CRGs score based on DEGs with significant prognostic differences was established to evaluate the prognosis and immunotherapeutic efficacy of UCEC patients. The CRGs score was shown to be useful in predicting clinical outcomes. Patients with a low CRGs score seemed to have a better prognosis, a better immunotherapeutic response, and a higher tumor mutation burden (TMB). In conclusion, our study explored the influence of cuproptosis patterns and TME on the prognosis of cancer patients, thereby improving their prognosis.

Introduction: Endometrial cancer is currently one of the three most common female reproductive cancers, which seriously threatens women’s lives and health. Hypoxia disrupts the tumor microenvironment, thereby affecting tumor progression and drug resistance.Methods: We established hypoxia-related gene model to predict patient prognosis and 1-, 3-, and 5-year overall survival rates. Then, the expression level of hypoxia-related genes and survival data were extracted for comprehensive analysis by Cox regression analysis, and the model was established.Results: We analyzed the survival and prognosis of patients in the high and low-risk groups. The Kaplan-Meier curve showed that the low-risk group is associated with a better survival rate. The 1-, 3-, and 5-year AUC values of the model were 0.680, 0.698, and 0.687, respectively. Finally, we found that LAG3 may be a potential immune checkpoint for endometrial cancer.Conclusion: We found four hypoxia-related genes (ANXA2, AKAP12, NR3C1, and GPI) associated with prognosis. The hypoxia-related gene model can also predict prognosis and tumor microenvironment in endometrial cancer.