Hypomethylated gene RAC3 induces cell proliferation and invasion by increasing FASN expression in endometrial cancer

Abstract

Background: Endometrial cancer (EC) is one of the most prevalent gynecological cancers with a 5-year survival rate of 20-60%. Feasible prognostic molecular biomarkers of EC are necessary for accurate prediction of EC prognosis.

Methods: RAC3 is a member of the Rho GTPases. Public databases including Gene Expression Profiling Interactive Analysis (GEPIA2), Tumor Immune Estimation Resource (TIMER), LinkedOmics, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), TISIDB and cBioPortal were employed to analyze the differential expression, clinicopathologic characteristics, functional networks, immune cell infiltrates and genetic alteration of RAC3 in EC patients.

Results: RAC3 expression was elevated in EC patients analyzed by TIMER and GEPIA. Overexpression of RAC3 was obviously correlated with clinical stage, histological type, histological grade and DNA hypomethylation. Patients with high RAC3 expression displayed poor overall survival. Functional enrichment analysis showed that RAC3 was involved in translational initiation, DNA replication and mRNA processing. RAC3 expression was negatively associated with infiltrating levels of B cells, CD8 + T cells, macrophages and dendritic cells in EC. Experiments in vitro showed that RAC3 was upregulated in EC tissues and cell lines, and RAC3 induced cell proliferation and invasion by increasing fatty acid synthase (FASN) expression.

Conclusion: High expression of RAC3iscorrelated with poor prognosis and low infiltration of immune cells in EC. RAC3 promotes cell proliferation and invasion via FASN. These results demonstrate thatRAC3 functions as an EC oncogene and reveal its underlying mechanism in EC progression, suggesting that RAC3 may serve as a potential therapeutic target in EC.

Keywords: Endometrial cancer; Immune infiltrates; Methylation; Prognosis; RAC3.