NAP1L1 Promotes Endometrial Cancer Progression via EP300-Mediated DDX5 Promoter Acetylation.

Abstract

Endometrial cancer is one of the predominant tumors of the female reproductive system. In this current study, we investigated the functions and related mechanisms of nucleosome assembly protein 1 like 1 (NAP1L1)/ DEAD-box helicase 5 (DDX5) in endometrial cancer. This retrospective study analyzed the medical records of patients with endometrial cancer, collected tissue samples for NAP1L1 and DDX5 staining, and conducted survival analysis using the Kaplan-Meier method. To evaluate the impact of NAP1L1 and/or DDX5 on cellular processes in endometrial cancer cells, several techniques were employed. These included Cell Counting Kit-8 assay, wound healing assay, Transwell assay, as well as overexpression or knockdown of target gene expression. Additionally, chromatin immunoprecipitation, dual luciferase reporter gene, and coimmunoprecipitation (Co-IP) assay were utilized to confirm the interaction between NAP1L1, E1A-binding protein p300 (EP300), and DDX5. Furthermore, qRT-PCR, Western blot, and Co-IP assay were performed to analyze the modulation of NAP1L1/DDX5 in Wnt/β-catenin. NAP1L1 and DDX5 expression were upregulated in endometrial cancer tissues, and correlated with poor prognosis. NAP1L1/DDX5 promoted endometrial cancer cell proliferation, migration, and invasion. NAP1L1 promotes acetylation and transcription by recruiting EP300 to the DDX5 promoter. DDX5 could activate Wnt/β-catenin signal by binding to β-catenin. In animal models, knockdown of NAP1L1 inhibits endometrial cancer tumor growth and lung metastasis. To sum up, our study demonstrated that NAP1L1 promoted the malignant phenotypes of endometrial cancer cells via recruiting EP300 to promote DDX5 acetylation, thus activating the Wnt/β-catenin signaling pathway. Implications: Our research findings indicate that targeting the NAP1L1/EP300/DX5 axis might be a new potential treatment option for endometrial cancer.