Clinical relevance of ARF/ARL family genes and oncogenic function of ARL4C in endometrial cancer

Members of ADP-ribosylation factor (ARF)/ARF-like protein (ARL) family regulate malignant phenotype of cancer cells. The present study aims to investigate the clinical relevance of ARF/ARL family members in endometrial cancer. We report that several ARF/ARL family genes serve as prognostic biomarkers for endometrial cancer. Through a combination of TCGA database and immunohistochemistry analysis, we revealed that ARL4C, a member of ARL family, was overexpressed in endometrial cancer and might function as an oncogene in endometrial carcinogenesis. Gene set enrichment analysis (GSEA) and functional studies demonstrated that cell cycle and cell adhesion pathways were the potential mechanism of ARL4C in promoting endometrial cancer cell proliferation, migration and invasion. Moreover, we also observed the involvement of ARL4C in metformin-inhibited cellular proliferation of endometrial cancer. Collectively, knowledge of the expression and function of ARF/ARL family genes could provide a potential therapeutic strategy for endometrial cancer.