Peihai Zhang

KDM6A Exhibits Antitumor Activities Toward Ovarian Cancer by Epigenetically Activating Transcription of ISG‐15

ABSTRACT Ovarian cancer (OC) is a leading cause of cancer‐related mortality among females worldwide. Lysine demethylase 6A (KDM6A) plays a crucial role in multiple physiological and pathological processes. However, its role in ovarian carcinogenesis remains unclear. The expression of KDM6A and survival analysis in OC were assessed utilizing GEPIA and Kaplan–Meier plotter databases. The expression of KDM6A was evaluated immunohistochemically in tissue samples from 55 OC patients. The CCK‐8, Colony formation, and Transwell assays were employed to assess the ability of OC cells in proliferation, migration, and invasion. Lung metastasis and subcutaneous tumor models were used to evaluate the function of KDM6A in vivo. RNA sequencing, Western blot, and quantitative polymerase chain reaction were conducted to investigate the molecular functions of KDM6A. A chromatin immunoprecipitation assay was employed to determine the effects of KDM6A on the promoters of ubiquitin‐like protein interferon‐stimulated gene 15 (ISG‐15). KDM6A expression was downregulated in OC and associated with poor progression‐free survival and overall survival. KDM6A inhibits OC cell proliferation, migration, and invasion in vitro. Xenograft models have also confirmed the antitumor role of KDM6A in OC growth and metastasis. The mechanistic study demonstrated that KDM6A exerted an antitumor effect in a histone‐demethylase‐dependent manner by epigenetically activating ISG‐15 transcription. KDM6A, a functional tumor suppressor, is frequently downregulated in OC. The KDM6A‐ISG‐15 axis is critical in restraining OC malignancy and may serve as a potential molecular target for novel therapies.

Overexpression of Stathmin 1 Predicts Poor Prognosis and Promotes Cancer Cell Proliferation and Migration in Ovarian Cancer

Purpose. The aim of this study was to investigate the expression of stathmin 1 (STMN1) in ovarian cancer and its effect on prognosis. The effect and mechanism of STMN1 on the proliferation and migration of ovarian cancer cells were also investigated. Methods. Expression of STMN1 was measured by immunohistochemical staining in ovarian cancer tissues. The effects of STMN1 on the proliferation and migration capacity of ovarian cancer were evaluated using Cell Counting Kit-8 (CCK-8) assays, colony formation assays, immunofluorescence staining, wound healing assays, and Transwell assays. Transcription factors were predicted by bioinformatic analysis of TCGA database. Results. STMN1 was upregulated in ovarian cancer tissues as compared to paracancerous tissues and associated with shorter overall survival. STMN1 expression significantly correlated with FIGO staging and tumor differentiation ( P < 0.05 ). Furthermore, STMN1 promoted proliferation and migration in ovarian cancer cell lines. Bioinformatic analysis revealed that STMN1 was potentially regulated by E2F transcription factors. Then, we found that E2F1 regulated the expression of STMN1 and affected proliferation. Conclusion. STMN1 is overexpressed in ovarian cancer, and its high expression suggests a poor prognosis. STMN1 promotes the proliferation and migration of ovarian cancer and is regulated by E2F1. Thus, STMN1 may serve as a negative prognostic factor and possible target for the treatment of ovarian cancer patients.