Transcriptional Activation of EGFL6 by E2F8 Promotes Proliferation, Migration, and Invasion in Endometrial Carcinoma Cell

BACKGROUND: Endometrial cancer (EC) posed a great threat to women's health, especially in postmenopausal women. E2F transcription factor 8 (E2F8), recognized as a central regulator of critical cellular processes, is overexpressed in endometrial carcinomas. However, the underlying mechanisms remains elusive and worthy of further investigation. Herein, we investigated whether E2F8 activates the expression of epidermal growth factor-like domain multiple 6 (EGFL6) through transcriptional regulatory mechanisms to regulate the occurrence and development of EC tumors. METHODS: Western blot and quantitative reverse transcription polymerase chain reaction (qPCR) analyses revealed the expression profiles of E2F8 and EGFL6 in tumor tissues and EC cells. The Ishikawa and KLE cell lines were selected as in vitro models of EC and were subsequently transfected with sh-E2F8 or overexpression EGFL6 (oe-EGFL6) plasmids. CCK-8 assay and Transwell assay were performed to evaluate the cell viability, migration, and invasion of EC cells. A dual luciferase assay was conducted to assess the interaction between E2F8 and EGFL6. E2F8-knockdown Ishikawa cells were subcutaneously transplanted to investigate their effect on EC tumor growth. RESULTS: E2F8 was greatly upregulated in EC cells. Silencing E2F8 inhibits the proliferation, migration, and invasion of EC cells, thereby suppressing tumor growth in vivo. Mechanistically, E2F8 transcriptionally activates EGFL6 by binding to its promoter. oe-EGFL6 rescues the impacts of E2F8 silencing on the proliferation, migration, and invasion of EC cells. CONCLUSION: These results indicated that E2F8 promotes proliferation, migration, and invasion of EC cells by transcriptionally activating EGFL6.