KIF15 knockdown inhibits the development of endometrial cancer by suppressing epithelial-mesenchymal transition and stemness through Wnt/β-catenin signaling.

Abstract

Endometrial cancer (EC) is one of the most common cancers among women, while the incidence of EC is rising. Many studies have found that Kinesin family member 15 (KIF15) is highly expressed in a series of cancers, but the role of KIF15 in EC is unclear. We detected the expression level of KIF15 in a microarray of EC tissues by immunohistochemical staining (IHC), and analyzed the correlation between the expression level of KIF15 and the pathological characteristics of patients. After inhibit the expression of KIF15 in EC cells with lentivirus, cell proliferation and apoptosis were detected respectively by CCK8 assay, flow cytometry and tunnel assay. Transwell assay and wound healing assay were used to examine the migration ability and invasion ability of EC cells. Spheroid formation assay was used to evaluate cell self-renewal ability. In vivo tumor xenograft model was used for validation. The expressions of epithelial-mesenchymal transition, cancer stem cells, and Wnt/β-catenin signaling molecules were detected by Western blotting. The results showed that the expression of KIF15 in EC tissues was higher than that in normal endometrial tissues, while the expression level of KIF15 in EC was positively correlated with the pathological grade of the tumor. The down-regulation of KIF15 reduced the proliferation, colony formation, invasion, migration and self-renewal ability of EC cells, while promoted cell apoptosis. Knockdown of KIF15 inactivates the Wnt/β-catenin signaling of EC cells, inhibitors of Wnt signaling can counteract the enhanced self-renewal ability caused by KIF15 overexpression. Therefore, KIF15 may be a new potential target for diagnosis and treatment of EC.

• Authors: Jie Huang, Xinwei Sun, Ge Diao, Runbo Li, Jianxin Guo, Jian Han
• Journal: Environmental toxicology (Environ Toxicol) Vol. 38 Issue 8 Pg. 1824-1834 (Aug 2023) ISSN: 1522-7278 [Electronic] United States
• PMID: 37186152 (Publication Type: Journal Article)
• Copyright: © 2023 The Authors. Environmental Toxicology published by Wiley Periodicals LLC.

Chemical References

• beta Catenin
• KIF15 protein, human
• Kinesins

Topics

• Humans
• Female
• beta Catenin (genetics, metabolism)
• Epithelial-Mesenchymal Transition (genetics)
• Wnt Signaling Pathway
• Cell Proliferation (genetics)
• Endometrial Neoplasms (genetics)
• Cell Line, Tumor
• Cell Movement (genetics)
• Gene Expression Regulation, Neoplastic
• Kinesins (genetics, metabolism)