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

Front Biosci (Landmark Ed). 2023 Dec 29;28(12):368. doi: 10.31083/j.fbl2812368.

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: EMT; RIPK4; biomarker; ovarian cancer; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Down-Regulation
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / metabolism
  • Protein Serine-Threonine Kinases* / genetics

Substances

  • RIPK4 protein, human
  • Protein Serine-Threonine Kinases