RIPK4 Promotes Cell Invasion and the Epithelial–Mesenchymal Transition in Ovarian Cancer

² Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, 361003 Xiamen, Fujian, China

³ Endoscopy Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, 361003 Xiamen, Fujian, China

⁴ Department of Radiation Oncology, Xiamen Cancer Center, Xiamen Key Laboratory of Radiation Oncology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, 361003 Xiamen, Fujian, China

^*Correspondence: wusg@xmu.edu.cn (San-Gang Wu); zhoujuan@xmu.edu.cn (Juan Zhou)
^†These authors contributed equally.

Front. Biosci. (Landmark Ed) 2023, 28(12), 368; https://doi.org/10.31083/j.fbl2812368

Submitted: 24 May 2023 | Revised: 10 September 2023 | Accepted: 19 September 2023 | Published: 29 December 2023

This is an open access article under the CC BY 4.0 license.

Abstract

Objective: To investigate the clinical role and biological function of receptor-interacting protein kinase 4 (RIPK4) in ovarian cancer (OC). Methods: We conducted a comprehensive analysis of the expression and prognostic role of RIPK4 in OC using various public databases including The Cancer Genome Atlas, Oncomine, and Kaplan–Meier plotter. In vitro studies included wound healing, cell migration and invasion, cell proliferation, and cell apoptosis assays as well as vascular mimicry experiments. In vivo studies were conducted using subcutaneous and intraperitoneal xenografts. Results: Our findings revealed that RIPK4 was significantly overexpressed in OC tissue compared to normal ovarian tissue. Moreover, the overexpression of RIPK4 was associated with advanced-stage disease and a poor prognosis in OC patients. RIPK4 silencing resulted in significant inhibition of intraperitoneal tumor growth, invasion, and vascular mimicry in OC cells. Furthermore, downregulation of RIPK4 inhibited the epithelial–mesenchymal transition of OC cells both in vitro and in vivo by promoting the expression of E-cadherin and inhibiting the expression of N-cadherin. Conclusion: The results of this study suggest that RIPK4 may function as an oncogene in the development and prognosis of OC.

Keywords

ovarian cancer

RIPK4

EMT

biomarker

prognosis

Funding

2022J011379/Natural Science Foundation of Fujian Province

2021GGB027/Commission Young and Middle-aged Talents Training Project of Fujian Health Commission

Figures

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Fig. 1.

The differentially expressed genes were obtained from databases and tissues. (A) Gene Expression Profiling Interactive Analysis (GEPIA) database. (B) Oncomine database. (C) The expression of receptor-interacting protein kinase 4 (RIPK4) in various cancers and normal tissue from the Oncomine database (blue represents low expression in cancers and red represents high expression in cancers). The deep color indicates ranking at the top. (D) Immunohistochemical staining of RIPK4 in ovarian cancer (OC) and normal ovarian tissues (magnification, 40 $\times{}$ ). The data are presented as the mean $\pm{}$ standard deviation (SD), and statistical significance is indicated as follows: *p $<$ 0.05.

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